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FOCUSED On advancing the next wave of
medicine for inflammatory diseases JUNE 2025 2025 THIRD HARMONIC BIO Exhibit 99.1
Forward Looking Statements This
presentation contains forward-looking statements within the meaning of, and made pursuant to the safe harbor provisions of, the Private Securities Litigation Reform Act of 1995. Any statements made in this presentation that are not statements of
historical fact, including, but not limited to, the dissolution and Plan of Dissolution, the timing and amount of any distribution to the Company's stockholders pursuant to the Plan of Dissolution, the Company's strategic review process,
and the Company's ability to enter into any agreements or transactions for the sale of its remaining assets and intellectual property, including THB335, or if entered into, that any such agreements or transactions will be successful or on
attractive terms. These statements often include words such as "anticipate," "expect," "suggests," "plan," "believe," "intend," "estimates," "targets,"
"projects," "should," "could," "would," "may," "will," "forecast" and other similar expressions. These forward-looking statements are contained throughout this
presentation. We base these forward-looking statements on our current expectations, plans and assumptions that we have made in light of our experience in the industry, as well as our perceptions of historical trends, current conditions, expected
future developments and other factors we believe are appropriate under the circumstances at such time. As you read and consider this presentation, you should understand that these statements are not guarantees of future performance or results. The
forward-looking statements are subject to and involve risks, uncertainties and assumptions, and you should not place undue reliance on these forward-looking statements. Although we believe that these forward-looking statements are based on
reasonable assumptions at the time they are made, you should be aware that many factors could affect our actual results or results of operations and could cause actual results to differ materially from those expressed in the forward-looking
statements. Factors that may materially affect such forward-looking statements include: our limited operating history and that we have not completed any clinical trials beyond Phase 1 and have not had any product candidates approved for commercial
sale; our significant net losses incurred since inception and the likelihood of incurring additional losses for the foreseeable future; our need for substantial additional funding; the early stage of development of our programs and the possibility
they may fail in development; our future performance is substantially dependent on our ability to identify and develop future product candidates; legal and regulatory risks; and intellectual property-related risks, among others. Additional risks and
uncertainties that could affect our financial results and business are more fully described under the caption "Risk Factors" in our Quarterly Report on Form 10-Q for the three months ended March 31, 2025, filed with the SEC on May 8,
2025, and our other SEC filings, which are available on the Investor & Media page of our website at https://ir.thirdharmonicbio.com/ and on the SEC's website at www.sec.gov. These cautionary statements should not be construed by you to be
exhaustive and are made only as of the date of this presentation. We undertake no obligation to update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise, except as required by applicable
law. This presentation also contains estimates and other statistical data made by independent parties and by us relating to market size and growth and other data about our industry. This data involves a number of assumptions and limitations, and you
are cautioned not to give undue weight to such estimates. In addition, projections, assumptions, and estimates of our future performance and the future performance of the markets in which we operate are necessarily subject to a high degree of
uncertainty and risk.
Summary and Next Steps
Liquidation and Dissolution on-track and sale process of THB335 underway Stockholders approved liquidation and dissolution of the Company Initial distribution currently expected in the range between approximately $5.30 and $5.35 per share of common
stock, expected in the third quarter of 2025 THB335 demonstrated 85% serum tryptase reduction with an encouraging safety profile in an additional Phase 1 cohort evaluating 100mg dose with new drug product capsule formulation Sale process of THB335
initiated Completed all clinical, toxicology and manufacturing activities to support a Phase 2 clinical trial of THB335 for the treatment of CSU; FDA submission imminent to seek clearance for trial initiation
"PIPELINE-IN-A-TARGET"
POTENTIAL CLINICAL CANDIDATE: THB335 KIT: A NOVEL, CLINICALLY VALIDATED TARGET LARGE ESTABLISHED MARKETS WITH HIGH UNMET NEED THRD: Focused on KIT to Treat Mast Cell-Mediated Inflammatory Diseases Millions of patients living with severe mast
cell-mediated diseases; high residual need despite multiple approved products Clinical validation of KIT as potentially transformative target for mast cell-mediated diseases Highly selective, oral small molecule with potential to optimize
therapeutic index and offer patient convenience over injectables Potential treatment options for a range of dermal, airway, and GI inflammatory diseases
Prevalence: More than 1.5 million
patients or 0.5-1% point prevalence; ~70-80% female, mean age ~46 years Disease impact: CSU severely impairs quality of life, causes significant physical discomfort and emotional distress, including anxiety, depression, insomnia and social isolation
Limited treatment options: Oral anti-histamines effective in only ~50% of patients; single biologic therapy approved for second-line use New treatment options are imperative to driving disease awareness, diagnosis and treatment High
Disease Burden in Chronic Spontaneous Urticaria A severe, yet undertreated dermal inflammatory condition "Out there, it's a horrible world for urticaria patients"1 1Marcus Maurer MD, LifeSci Immunology and Inflammation Day, May 10,
KIT is the Master Regulator of Mast
Cell Function and Survival Oral small molecule approach to KIT offers multiple potential therapeutic advantages KIT Targeting mast cell vs specific activating pathways or downstream mediators provides broad approach to addressing disease
symptoms Emerging clinical validation for potential best-in-disease efficacy in CSU Dimerization SCF dimer KIT receptor P P P P P P Intracellular Small Molecule Inhibition Potential for therapeutic index optimization Patient and medical practice
convenience Avoids risk of mAb-mediated mast cell activation/anaphylaxis Allergen IgE Other stimuli Cytokines THB335 (KIT inhibitor) KIT inhibitor reduces mast cell proliferation, differentiation, and survival KIT inhibitor reduces mast cell
THB335: A Next-Generation, Potent, and
Highly Selective Wild-Type KIT Inhibitor Low nanomolar KIT potency with excellent kinome selectivity in biochemical and cell-based assays Peripherally restricted biodistribution Structural and metabolic improvements vs THB001 to address DILI risk
Favorable nonclinical pharmacokinetic profile, including high oral bioavailability, metabolic stability, and long circulating half-life No off-target toxicology findings in IND-enabling studies, consistent with THB001 experience through chronic
studies in rodent and non-rodent species New composition of matter IP; base patent term through 2043 THB335 Product Profile DILI = drug-induced liver injury
THB335 In Vitro Pharmacology Overview
Potent, selective, reversible KIT kinase inhibitor DiscoverX KinomeSCAN @ 1 M KIT Biochemical Cellular Kinase Target KD (nM) HTRF KIT IC50 (nM) Multiple (nM) KIT 1.5 16.1 5.01 - 7.92 CSF1R 33 56 >30003 -
>100002 PDGFR NT 2710 NT PDGFR 34 737 >30004 ABL1 NT NT >100002 DDR1 NT NT 78002 FLT3 >1000 NT NT Percent Control 0% 0.1% 0.1-1% 1-5% 10-35% > 35% 5-10% 1 M-07e pKIT IC50 (KIT) 2 HEK293 nanoBRET EC50 (KIT, CSF1R, ABL1,
DDR1) 3 M-NFS-60 EC50 (CSF1R) 4 A10 EC50 (PDGFR )
THB335: Phase 1 SAD/MAD/Food Effect in
Healthy Volunteers Assess safety and tolerability Characterize pharmacokinetics Measure pharmacodynamic effect by serum tryptase Key Objectives Phase 1 Trial Design Single Ascending Dose (n=40) (fasted unless otherwise specified) Healthy
Male/Female, 18-65 yrs Plasma PK Serum Tryptase Multiple Ascending Dose (n=39) Healthy Male/Female 18-65 yrs Plasma/Urine PK Serum Tryptase 164 mg 41 mg 82 mg 21 mg 205 mg Fed 164 mg 41 mg 82 mg 21 mg fasted fed fed fed 1 2 3 4 5 1 2 3 5 100 mg fed
4 Gen 1 Gen 2 Drug Product Capsule Formulation
Additional THB335 Phase 1 100mg MAD
Cohort Key changes vs original Phase 1 trial MAD cohorts Utilized a new drug product capsule formulation that is intended for use in future clinical development (Gen 2) vs FIH API in capsule used for original Phase 1 cohorts (Gen 1) Lab draws
decreased by ~1/2 to minimize phlebotomy effect seen in original Phase 1 cohorts Enrollment increased from n=8 (6 active, 2 placebo) to n=10 (7 active, 3 placebo) 14-day dosing period maintained; subjects monitored in-unit through day 28 Baseline
thresholds introduced for ANC (3000/uL) and hemoglobin (13.0 g/dL) ANC = absolute neutrophil count; FIH = first-in-human; API = active pharmaceutical ingredient
THB335 100mg MAD Cohort
Pharmacokinetics Summary Consistent PK with 164mg dose level in original MAD cohort of the Phase 1 trial THB335 MAD PK 1 One subject discontinued at day 3 due to unrelated hypertension THB335 Plasma Conc (ng/mL) Time (day) Dose KIT IC90 Coverage
Placebo (n=3) N/A Gen 2 100 mg (n=7) ~7.4x Gen 1 164 mg (n=5)1 ~6.8x 100 mg
THB335 100mg MAD Cohort
Pharmacodynamics Summary - Serum Tryptase Consistent serum tryptase reductions with 164mg dose level in original MAD cohort of the Phase 1 trial Dose Serum Tryptase Mean % Reduction at Day 15 Placebo (n=3) -16% Gen 2 100 mg (n=7) -85% Gen 1
164 mg (n=5)1 -84% Placebo 100 mg THB335 MAD Serum Tryptase Avg (percent change from baseline) Study day Tryptase values below lower limit of quantification (LLOQ; 1 ng/mL) were imputed at 0 ng/mL 1 One subject discontinued at day 3 due to unrelated
THB335 100mg MAD Cohort Safety
Summary Adverse events reported 2 subjects 100 mg N=7 Placebo N=3 Pruritus 3 0 Somnolence 3 0 Abdominal distension 2 0 Constipation 2 0 Erythema 2 0 Flatulence 2 0 Muscle spasms 2 0 Pain in extremity 2 0 One moderate AE of neutrophil
reduction; known on-target effect of KIT inhibition No AEs due to hemoglobin reduction; no clinically significant laboratory value changes One subject experienced mild hair color change and mild taste loss No discontinuations due to drug-related
THB335 100mg MAD Cohort Safety:
Hemoglobin and ANC No adverse events related to hemoglobin Expected on-target dose-dependent reductions in ANC; one moderate adverse event Hemoglobin (g/dL) Mean value Study day ULN LLN LLN ULN Neutrophils (absolute) (Thou/uL) Mean value Study day
ULN LLN Placebo 100 mg Placebo 100 mg Placebo 100 mg
Original Phase 1 MAD Cohorts
Previously Presented Data
THB335 MAD Pharmacokinetics Summary
T1/2 ~40 hours Mild positive food effect 41% variability coefficient THB335 MAD PK 21 mg 41 mg 82 mg 164 mg THB335 plasma concentration (ng/mL) Time (days) IC90 IC50 Dose KIT IC90 Coverage Placebo (n=8) na 21 mg (n=6) ~0.5x 41 mg (n=6) ~2x 82 mg
(n=6) ~4.5x 164 mg (n=5)1 ~6.8x 1 One subject discontinued at day 3 due to unrelated hypertension
THB335 MAD Pharmacodynamics Summary
- Serum Tryptase Dose Serum Tryptase Mean % Reduction at Day 15 Placebo (n=8) 0.8% 21 mg (n=6) -13% 41 mg (n=6) -50% 82 mg (n=6) -59% 164 mg (n=5)1 -84% Tryptase values below lower limit of quantification (LLOQ; 1 ng/mL) were imputed at 0
ng/mL 1 One subject discontinued at day 3 due to unrelated hypertension THB335 MAD Serum Tryptase Placebo 21 mg 41 mg 82 mg 164 mg Avg (percent change from baseline) Visit day Tryptase concentrations (ng/mL)
THB335 MAD Pharmacodynamics Summary
- Stem Cell Factor THB335 MAD Stem Cell Factor Dose Stem Cell Factor Mean % Increase at Day 16 Placebo (n=8) 0.4% 21 mg (n=6) 9% 41 mg (n=6) 23% 82 mg (n=6) 43% 164 mg (n=5)1 56% 1 One subject discontinued at day 3 due to unrelated
hypertension Mean/SD Percent Change from Baseline Visit day Placebo 21 mg 41 mg 82 mg 164 mg
THB335 MAD Safety Summary Adverse
events reported 2 subjects AE TERM Dose 21 mg 41 mg 82 mg 164 mg Placebo Hair Depigmentation 0 0 3 4 0 Low Hemoglobin 0 0 2 5 0 Decreased WBC 0 1 1 2 0 Low ANC 0 1 0 2 0 Elevated Liver Enzymes 0 0 0 1 2 Headache 0 1 0 0 1 Contact
Dermatitis due to EKG leads 1 0 0 0 1 Hair depigmentation, low hemoglobin and decreased neutrophils (ANC)/white blood cell (WBC) counts all known on-target effects of KIT inhibition All adverse events resolved either during dosing or after dosing
completion during follow-up period No discontinuations due to drug-related adverse events
THB335 MAD Safety: ALT/AST
Elevations Mild/moderate, asymptomatic and transient transaminase elevations in 3 subjects (2 placebo, 1 active) Numeric result Study day ALT (U/L) AST (U/L) Placebo (21 mg cohort) Placebo (164 mg cohort) Active (164 mg cohort) High In range ALT
>500 U/L is international standard for evidence of drug-induced liver injury 164 mg cohort AEs are largely consistent in time course and similar in magnitude between active and placebo subjects 164 mg active subject's liver values began to
decline by day 15, when THB335 exposure remained high Plasma metabolite ID showed no evidence for presence of reactive intermediates Based on data review with DILI experts, transaminitis event in active subject not believed to be
Expected on-target dose-dependent
reductions in ANC All values normalized by follow-up day 38 THB335 MAD Safety: Neutrophils (ANC) Neutrophils (absolute) ANC (109/L) 21 mg 41 mg 82 mg 164 mg Placebo ULN ULN LLN Visit day Mean value
Hemoglobin (g/dL) THB335 MAD
Safety: Hemoglobin 21 mg 41 mg 82 mg 164 mg Placebo Evidence of phlebotomy effect in decreased hemoglobin in placebo subjects Lower baseline values in 164 mg cohorts may contribute to AE severity ULN LLN LLN ULN Mean value Visit day
THB335 MAD Hematology Safety
Summary AE TERM Severity Dose 21 mg 41 mg 82 mg 164 mg Low hemoglobin Mild 0 0 0 0 Moderate 0 0 2 2 Severe 0 0 0 3 Low ANC Mild 0 0 0 0 Moderate 0 1 0 1 Severe 0 0 0 1 Low WBC Mild 0 1 1 1 Moderate 0 0 0 1 Severe 0 0 0 0 Hemoglobin AEs graded
utilizing FDA preventative vaccine clinical trial guidance1 AEs graded utilizing CTCAE2 criteria in THB001 Phase 1 study (conducted ex-US) All hemoglobin AEs reported in this study are grade 1 under CTCAE guidelines 1
THB335 MAD Safety: Hemoglobin Mean
Hemoglobin (SD) (g/dL) Day 1 Day 14 Day 22 Day 29/EOS Placebo (n=8) 12.9 (1.22) 12.8 (1.11) 12.2 (1.18) 12.6 (0.93) 21 mg (n=6) 12.8 (0.56) 12.4 (0.55) 12.2 (0.53) 12.3 (0.72) 41 mg (n=6) 14.2 (0.95) 14.0 (1.35) 13.1 (1.19) 13.4 (1.01) 82 mg (n=6)
14.0 (0.68) 12.7 (0.67) 12.1 (0.63) 12.7 (0.55) 164 mg (n=5)1 12.9 (0.63) 12.3 (0.70) 10.8 (0.56) 11.6 (0.69) Majority female study population drives lower baseline/day 1 values Hemoglobin values nadir at day 22, evidence of partial recovery by day
29 AE grading per FDA vaccine guidance (change from baseline) Grade 2 (moderate): 1.6-2.0 g/dL Grade 3 (severe): 2.1-5.0 g/dL 1 One subject discontinued at day 3 due to unrelated hypertension
THB335 Phase 1 Clinical Trial
Results Summary Once daily dosing with dose-dependent increases in exposure exceeded the KIT IC90 at doses > 41mg Sustained, dose-dependent decreases in serum tryptase Most recent clinical data demonstrates encouraging safety profile with minimal
on-target adverse events Provides basis for a Phase 2 clinical trial in CSU