Dianthus Therapeutics, Inc. · NASDAQ:DNTH
Dianthus Therapeutics — Investor Presentation (December 2024)
31 slides from Dianthus Therapeutics's investor presentation, Dec 12, 2024
Slide 1: Corporate Presentation December 2024
Corporate Presentation December 2024 Exhibit 99.1
Slide 2: Forward-Looking Statements
FORWARD-LOOKING STATEMENTS Certain statements in this presentation (“Presentation”), other than purely historical information, may constitute “forward-looking statements” within the meaning of the federal securities laws, including for purposes of the safe harbor provisions under the United Stated P
Slide 3: DNTH103 lead program and company highlights
Lead program, DNTH103, is a potent investigational monoclonal antibody that targets the classical complement pathway by selectively inhibiting active C1s protein Top-line Ph. 1 data confirm a ~60-day half-life, potent classical pathway inhibition, and a potentially differentiated safety profile Cash
Slide 4: DNTH103 offers pipeline in a product across neuromuscular indications
DNTH103 offers pipeline in a product, best-in-class potential in multiple neuromuscular indications Generalized Myasthenia Gravis Multi-billion $ market today, with opportunity for a differentiated complement inhibitor to further penetrate and expand first-line biologics use Chronic Inflammatory Dem
Slide 5: gMG represents a multi billion-dollar opportunity
gMG represents a multi billion-dollar opportunity with only two approved classes, each with room to improve U.S. gMG estimated patient population: ~60,000 $ in millions. Soliris & Ultomiris 2021 sales account for 1/1 – 6/30 & 7/21 – 12/31. Evaluate Pharma https://www.mgregistry.org/, https://www.ncb
Slide 6: CIDP: neuromuscular indication with high unmet medical need
Neuromuscular indication with high unmet medical need Evidence supports classical complement role in disease CIDP is an attractive opportunity with clinical PoC demonstrated by riliprubart, an active-C1s inhibitor IND cleared by FDA to initiate pivotal Phase 3 trial of DNTH103; DNTH103 target dose o
Slide 7: DNTH103 has superior affinity and potency vs. riliprubart
DNTH103 has superior affinity and potency vs. riliprubart Note: Riliprubart is produced using sequence from patent WO2018071676A1 1 Data shown is dissociation constant (KD) and the average of 3 different experiments performed at independent laboratories 2 Data is quantitative analysis of active C1s
Slide 8: MMN: neuromuscular indication with high unmet medical need
Neuromuscular indication with high unmet medical need Evidence supports classical complement role in disease MMN is an attractive opportunity with clinical PoC demonstrated via classical pathway inhibition Phase 2 trial of DNTH103, a low-volume Q2W S.C., ongoing in MMN No approved targeted biologic
Slide 9: Key differentiators of DNTH103 versus C2 inhibitor in MMN
Considerations Key Differentiators of DNTH103 MMN is an IgM and classical pathway driven disease1 C2 inhibitor that targets classical and lectin pathways Active C1s inhibitor targeting classical pathway only Demonstrated potent classical pathway inhibition with target dose achieving >IC90 on CH50 he
Slide 10: DNTH103 rapidly advancing in three clinical trials
Program (Target) Target Population 2024 2025 2026 DNTH103 (S.C. Active C1s antibody) Generalized Myasthenia Gravis (gMG) ~60,000 U.S. patients Multifocal Motor Neuropathy (MMN) ~5,000-10,000 U.S. patients Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) >40,000 U.S. patients DNTH103 is rapid
Slide 11: Opportunity in Myasthenia Gravis
DNTH103 Opportunity in Myasthenia Gravis
Slide 12: DNTH103 target product profile differentiated vs. approved biologics for gMG
DNTH103 Lower volume, less frequent, self-administered S.C. More frequent and/or higher-volume, in-clinic I.V. Need for increased convenience and reduced patient burden DNTH103 target product profile is highly differentiated vs. currently approved biologics for gMG 1 Can be self-administered daily v
Slide 13: Targeting C1s preserves lectin and alternative pathways
Membrane Attack Complex (MAC) Targeting C1s preserves critical immune activity of lectin and alternative pathways, with the aim to provide a safer therapeutic option versus terminal pathway inhibitors Complement inhibitors are well established in gMG and other severe autoimmune disorders Downstream
Slide 14: C1s is a clinically validated target in the classical pathway
C1q lgG antibody Cell Surface C1s is a clinically validated target in the classical complement pathway with an FDA approved therapy The C1 complex The initial component of the classical complement pathway consisting of C1q, C1r and C1s 3 2 2 3 Active C1s A serine protease that executes catalytic fun
Slide 15: DNTH103 designed with best-in-class properties
DNTH103 exploits validated C1s biology and has been designed with best-in-class properties Extended half-life Validated YTE half-life extension technology applied Clinical data demonstrates half-life of ~60 days Novel IP Patent applications for composition of matter and method of use expected to exp
Slide 16: Clinical Development
DNTH103 Clinical Development
Slide 17: DNTH103 Phase 1 healthy volunteer study design
SAD 1 (1 mg/kg) SAD 3 (30 mg/kg) SAD 2 (10 mg/kg) MAD 1 Q2W (300 mg) MAD 2 Q2W (600 mg) SAD 1 (300 mg) SAD 2 (600 mg) I.V. Administration S.C. Administration S.C. Administration SAD MAD DNTH103 Phase 1 healthy volunteer study was designed to validate extended half-life, potency and safety 44 HVs enr
Slide 18: DNTH103 demonstrated deep and sustained complement inhibition in healthy volunteers
DNTH103 has demonstrated deep and sustained complement inhibition in healthy volunteers DNTH103 demonstrated a ~60-day half-life and IC90 of 87 µg/mL I.V. SAD: Linear PK with Exposure Proportional Across Doses S.C. MAD: Strong Accumulation with Q2W Dosing PK/PD: Analysis Demonstrates IC90 of 87 µg/m
Slide 19: Phase 1 data confirms potent classical pathway inhibition as Q2W S.C. injection
15mg/kg I.V. on Day 0 300mg S.C. Q2W starting Day 7 DNTH103 Phase 1 data confirms potent inhibition of the classical pathway as a Q2W S.C. injection ~60-day half-life IC90 calculated at 87 µg/mL Ph. 1 Data Confirms Simulation using data from 60 healthy volunteers dosed across multiple cohorts demons
Slide 20: DNTH103 was generally well tolerated in Phase 1
DNTH103 was generally well tolerated, with a favorable safety profile in Phase 1 No standard safety lab findings (hematology, chemistry, coagulation LFTS and renal function) No serious adverse events No infection adverse event signal and no infections related to encapsulated bacteria Five participan
Slide 21: S.C. gMG Phase 2 trial design
DNTH103 S.C. gMG Phase 2 trial initiated in Q1’24 A global, multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety, efficacy, and PK / PD of DNTH103 administered S.C following initial loading dose Top-line data expected in 2H’25 If successful, path to BLA expected to
Slide 22: S.C. MMN Phase 2 trial design
DNTH103 S.C. MMN Phase 2 trial initiated in Q3’24 A global, multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety, efficacy, and PK / PD of DNTH103 administered S.C following initial loading dose Top-line data expected in 2H’26 300mg and 600mg S.C. Q2W dosing surpass
Slide 23: CIDP Phase 3 trial design and interim responder analysis
CIDP interim responder analysis anticipated 2H’26 CIDP Phase 3 trial designed as a two-part, randomized withdrawal, double-blind, placebo-controlled trial to evaluate the efficacy and safety of DNTH103 300mg and 600mg administered S.C Q2W DNTH103 300mg S.C. Q2W N=64 Placebo N=64 DNTH103 600mg S.C. Q
Slide 24: Corporate
Corporate
Slide 25: Three clinical trials ahead of Phase 2 gMG readout; strong balance sheet
2024 2025 2026 DNTH103 (S.C. Active C1s) gMG MMN CIDP Key External Catalysts Key External Catalysts Q1 Initiated Ph. 2 trial Three clinical trials for DNTH103 ahead of transformative Phase 2 gMG readout Strong balance sheet with ~$343M1 of cash and runway into the second half of 2027 ~34.3M shares o
Slide 26: Senior Management and Board of Directors
SENIOR MANAGEMENT Accomplished team of biotech industry veterans and scientists committed to bringing innovation to market Select Experience Includes: Simrat Randhawa, M.D. Chief Medical Officer Marino Garcia President & CEO Adam Veness, Esq. General Counsel Kristina Maximenko Chief People Officer B
Slide 27: Appendix
Appendix
Slide 28: DNTH103 improves neurotransmission and muscle contraction in AChR+ MG model
DNTH103 improves neurotransmission and muscle contraction in an AChR+ MG model Results provide further scientific rationale for DNTH103 in gMG Serum from MG patients used in a validated in vitro MG model1,2,3 Assessed improvement in neurotransmission and muscle contraction of ravulizumab* and DNTH10
Slide 29: In vitro study shows lower risk of Neisseria meningitidis infections
DNTH103 in vitro study demonstrates lower risk of Neisseria meningitidis infections Anti-capsular antibody (Anti -Nm) mimics N. meningitidis vaccination 0 50 100 150 % Bacterial Survival Serum +Anti - Nm 0.3 uM 1.0 uM DNTH103 Anti - C5 No treatment Results further validate the differentiated safety
Slide 30: C5 inhibitor Ultomiris carries FDA Boxed Warning and REMS requirement
C5 inhibitor Ultomiris carries FDA Boxed Warning and REMS requirement Source: ULTOMIRIS prescribing information & https://ultomirishcp.com/-/media/Ultomiris_NMOSD_hcp/full-site/pdfs/nmosd-ultomiris-rems-patient-safety-card
Slide 31: DNTH103 restores neuronal conduction velocity in in vitro CIDP model
DNTH103 restores neuronal conduction velocity in an in vitro CIDP model Results provide further scientific rationale for DNTH103 in CIDP Serum from 3 CIDP patients was evaluated in a validated, commercially available in vitro CIDP model1 Assessed improvement in neuronal conduction velocity of two do
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