UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM
CURRENT REPORT
Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): |
(Exact name of Registrant as Specified in Its Charter)
(State or Other Jurisdiction |
(Commission File Number) |
(IRS Employer |
||
|
|
|
|
|
|
||||
|
||||
(Address of Principal Executive Offices) |
|
(Zip Code) |
||
Registrant’s Telephone Number, Including Area Code: |
|
(Former Name or Former Address, if Changed Since Last Report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
|
|
|
Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
|
|
|
Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
|
|
|
Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
Securities registered pursuant to Section 12(b) of the Act:
|
|
Trading |
|
|
|
|
The |
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).
Emerging growth company
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
Item 8.01 Other Events.
On December 12, 2024, Dianthus Therapeutics, Inc. posted an updated corporate presentation (the "Presentation") on the investor relations section of its website. The Presentation is filed as Exhibit 99.1 and is incorporated by reference into this Item 8.01.
Cautionary Note Regarding Forward-Looking Statements. The Presentation contains forward-looking statements that involve certain risks and uncertainties that could cause actual results to differ materially from those expressed or implied by these statements. Please refer to the cautionary notes in the Presentation regarding these forward-looking statements.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits
Exhibit No. |
|
Description |
|
|
|
99.1 |
|
Corporate Presentation of Dianthus Therapeutics, Inc., dated December 2024 |
104 |
|
Cover Page Interactive Data File (embedded within the inline XBRL document) |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
|
|
|
DIANTHUS THERAPEUTICS, INC. |
|
|
|
|
Date: |
December 12, 2024 |
By: |
/s/ Adam M. Veness, Esq. |
|
|
|
Adam M. Veness, Esq. |
Corporate Presentation December 2024 Exhibit 99.1
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 Private Securities Litigation Reform Act of 1995, concerning Dianthus Therapeutics, Inc. (the “Company”). These forward-looking statements include statements regarding the Company’s future plans and prospects, including statements regarding the expectations or plans for discovery, preclinical studies, clinical trials and research and development programs, in particular with respect to DNTH103, and any developments or results in connection therewith, including the target product profile of DNTH103; the anticipated timing of the results from those studies and trials; expectations regarding the use of proceeds and the time period over which the Company’s capital resources will be sufficient to fund its anticipated operations; and expectations regarding the market and potential opportunities for complement therapies, in particular with respect to DNTH103. DNTH103 is an investigational agent that is not approved as a therapy in any indication in any jurisdiction worldwide. The words “opportunity,” “potential,” “milestones,” “runway,” “will,” “anticipate,” “achieve,” “near-term,” “catalysts,” “pursue,” “pipeline,” “believe,” continue,” “could,” “estimate,” “expect,” “ intend,” “may,” “might,” “plan,” “possible,” “predict,” “project,” “ should,” “ strive,” “would,” “aim,” “target,” “commit,” and similar expressions (including the negatives of these terms or variations of them) generally identify forward-looking statements, but the absence of these words does not mean that statement is not forward looking. Actual results could differ materially from those included in the forward-looking statements due to various factors, risks and uncertainties, including, but not limited to, that preclinical testing of DNTH103 and data from clinical trials may not be predictive of the results or success of ongoing or later clinical trials, that the development of DNTH103 or the Company's compounds may take longer and/or cost more than planned, that the Company may be unable to successfully complete the clinical development of the Company’s compounds, that the Company may be delayed in initiating, enrolling or completing any clinical trials, and that the Company's compounds may not receive regulatory approval or become commercially successful products. These and other risks and uncertainties are identified under the heading "Risk Factors" included in the Company's Annual Report on Form 10-K for the period ended December 31, 2023, and other filings that the Company has made and may make with the SEC in the future. Nothing in this Presentation should be regarded as a representation by any person that the forward-looking statements set forth herein will be achieved or that any of the contemplated results of such forward-looking statements will be achieved. Dianthus undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law.
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 runway expected to fund operations into 2H’27 DNTH103 intended to be the first subcutaneous, self-administered injection dosed as infrequently as once-every-two-weeks to treat generalized Myasthenia Gravis Top-line Ph. 2 results anticipated for gMG in 2H’25 and for MMN in 2H’26; interim responder analysis for pivotal Ph. 3 CIDP trial anticipated in 2H’26 Founded in 2019 to develop next-generation complement therapies to treat severe autoimmune diseases Advancing next-generation complement therapies to improve the lives of autoimmune disease patients Clinical proof-of-concept for classical pathway inhibition demonstrated in gMG, CIDP and MMN, validating the pipeline-in-a-product potential of DNTH103
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 Demyelinating Polyneuropathy Sanofi Ph. 2 riliprubart efficacy validates active C1s MoA Multifocal Motor Neuropathy Empasiprubart, an I.V. C2 inhibitor, validates classical pathway demonstrating efficacy in MMN patients gMG: https://www.mgregistry.org/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033452/# CIDP: IQVIA Claims Data; Riliprubart Phase 2 at EAN 2024 MMN: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3983019/ Highly selective to classical pathway Potent active C1s inhibitor 60-day half-life observed in clinic Consistent, infrequent dosing Convenient, S.C. intended for self-admin. via autoinjector Differentiated safety profile DNTH103’s Potentially Best-in-Class Properties: Clinical Development & Commercial Synergies ~60,000 U.S. patients ~5,000-10,000 U.S. patients Ph. 2 ongoing >40,000 U.S. patients Ph. 2 ongoing FDA cleared IND for Ph. 3
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.ncbi.nlm.nih.gov/pmc/articles/PMC7033452/# 1 Approved in gMG, aHUS, NMOSD, PNH; 2 Wall Street research estimate; 3 Astra Zeneca Q1 2024 results gMG driving Y/Y Ultomiris growth; U.S. growth driven by naïve gMG patients3 Soliris Ultomiris Soliris & Ultomiris1 >$6B in sales and growing; ~1/3 in gMG2 (only I.V.) Vyvgart I.V. sales in gMG showed rapid growth Estimated gMG peak sales >$3B; S.C. approved in June ‘23 CY’22: $401M Complement Class FcRn Class CY’23: $1.2BN
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 of 300mg/2mL S.C. every two weeks may offer more convenient, lower volume dosing for CIDP patients >40,000 patients in the U.S. and no approved targeted complement therapies riliprubart (active C1s inhibitor) recently reported positive interim efficacy results1 Riliprubart Phase 2 at PNS 2024 Pg 76: riliprubart patent filing Sanofi Ph. 2 riliprubart (SAR445088) data validates active C1s in CIDP1; Maintenance regimen of 600mg/4mL S.C. weekly2
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 protease inhibition of cleaved C4 fragments in the presence of DNTH103 or riliprubart 3 Data shown are the average of 3 experiments conducted for each of the functional assays (CH50 hemolysis, Wieslab and Liposome). CH50 and Wieslab were confirmed at independent laboratories DNTH103 riliprubart IC90 (nM) 0.47 3.69 C4 cleavage by human active C1s2 Enzymatic assay Functional assays of classical pathway inhibition DNTH103 riliprubart IC90 (ug/mL) 0.45 5.4 Wieslab classical pathway Assay in human serum3 CH50 assay of RBC lysis in human serum3 DNTH103 riliprubart IC90 (ug/mL) 98 668 DNTH103 riliprubart Fold Improvement Binding Affinity to human active C1s (KD)1 KinExa 9pM 75pM ~8X SPR 8pM 35pM ~4X Affinity assays DNTH103 consistently outperforms riliprubart in affinity and potency when compared head-to-head across multiple in vitro experiments ~8X more potent at blocking complement cascade ~12X more potent at IC90 ~7X more potent at IC90 DNTH103 riliprubart IC90 (ug/mL) 14.7 39.8 Liposome lysis in human serum3 ~3X more potent at IC90
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 therapies Empasiprubart (I.V., C2 inhibitor) recently reported efficacy signals1 MMN patient sera has been confirmed to activate complement ~5,000 - 10,000 patients in the U.S. https://www.argenx.com/sites/default/files/event-attachment/argenx_RnD_Day_2024_Slides.pdf#page=127 Empasiprubart (Q1-2W I.V., C2 inhibitor) Demonstrating Efficacy Signals1 “We hypothesize that targeting the classical complement pathway is a potential therapeutic approach in MMN. We investigated the interaction of circulating anti-GM1 IgM from patients with MMN with complement in detail using iPSC-derived MNs. In this disease model for MMN, we evaluated the effects of ARGX-117, a novel monoclonal antibody that inhibits complement factor C2.” - Neurol Neuroimmunol Neuroinflamm. 2022 Jan; 9(1): e1107 Placebo EMPA IV
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 hemolytic assay Lectin pathway critical to fight against bacterial infections2 Targets classical and lectin pathways Selective for classical pathway only, leaving lectin and alternative pathways intact Preserves key bacterial killing role of lectin pathway2 Convenient dosing and administration I.V. QW or I.V Q2W Target dose of 300mg/2mL S.C. Q2W More convenient by targeting infrequent, low volume, self-administered S.C. autoinjector DNTH103 profile has several advantages over a C2 inhibitor for the potential treatment of MMN * DNTH103 and empasiprubart are investigational agents that are not approved as therapies for MMN or any indication in any jurisdiction worldwide Budding K, et al. (2021). Neurol Neuroimmunol Neuroinflamm.9(1):e1107; Vlam L, et al. (2015). Neurol Neuroimmunol Neuroinflamm. 2015;2(4):e119 Ali YM, et al. (2012). PLoS Pathog 8(7):e1002793 DNTH103 (active C1s)* Empasiprubart (C2)* DNTH103 is differentiated given its strong biological rationale, safety profile, and patient convenience
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 rapidly advancing in three clinical trials, with data readouts beginning in 2H’25 Initiated Ph. 2 trial Q1’24 Top-line Ph. 2 data 2H’25 Initiated Ph. 2 trial Q3’24 IND cleared in Q4’24 for Ph. 3 trial DNTH103 has potential to expand into multiple classical pathway-driven diseases with its best-in-class profile Top-line Ph. 2 data 2H’26 gMG: https://www.mgregistry.org/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033452/# MMN: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3983019/ CIDP: IQVIA Claims Data; Riliprubart Phase 2 at EAN 2024 Interim Responder Analysis 2H’26
DNTH103 Opportunity in Myasthenia Gravis
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 via pre-filled syringe Daily self-administration or higher-volume S.C. administered by health care professional
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 complement inhibitors carry the risk of serious bacterial infections resulting in FDA Boxed Warnings Lectin pathway Mannan or pathogen surface Alternative pathway Pathogen surface C3 Convertase Shared terminal pathway (C5) Classical pathway Antibody-antigen complex Active form selectively inhibited by DNTH103 C1q, C1r, C1s gMG, MMN and CIDP are indications driven by autoantibodies that activate the complement system
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 function of the C1 complex, leading to MAC formation C1s is the only target of the C1 complex with an FDA approved therapy Enjaymo®, FDA approved in 2022 for CAD, is a C1s inhibitor but is not selective to the active form and dosed I.V. at 6,500-7,500mg every two weeks Enjaymo® information sourced from prescribing information 1 Classical pathway The only pathway activated by the presence of IgG and IgM, which bind to the C1 complex 1 Active C1s inhibition has recently demonstrated clinical benefit in CIDP Riliprubart results show clinical PoC for inhibiting active C1s in autoimmune neuromuscular diseases
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 expire no earlier than 2043 Low volume S.C. delivery Successful manufacturing of 150mg/mL formulation Low viscosity Favorable stability profile DNTH103 Target Product Profile S.C. self-administration 300mg in a 2mL pre-filled auto-injector suitable for convenient, self-administration Infrequent dosing Q2W dosing interval High selectivity and potency >10,000-fold binding affinity for Active C1s versus proC1s Picomolar binding affinity
DNTH103 Clinical Development
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 enrolled into six cohorts: Placebo (N= up to 2) Treated (N= up to 6) 16 HVs enrolled into two cohorts: Placebo (N= up to 2) Treated (N= up to 6) SAD MAD Safety, PK, and PD measured by percent classical pathway inhibition quantified in each cohort Key Parameters In completed cohorts, 60 healthy volunteers completed dosing as of December 2023 SAD 4 (50 mg/kg)
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/mL Data comprised of 60 HVs from 8 cohorts
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 demonstrates potent inhibition with infrequent S.C. dosing IC90 – 87 µg/mL Day 0: 15mg/kg I.V. Starting Day 7: 300mg S.C. Q2W Dosing Modeled
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 participants experienced mild/moderate Treatment Related AEs Two participants (one in each 300mg and 600mg S.C. MAD cohorts) had a mild or moderate injection site reactions (ISRs); no intervention was required and both participants completed treatment One participant experienced several non-specific AEs during infusion; infusion was paused for 8 minutes and restarted at the same rate without sequelae Two participants in 50mg/kg SAD I.V.1 cohort became ANA2 positive at Day 57; both participants had no evidence of SLE and both tested negative for dsDNA3 One participant in 600mg S.C. SAD reported vomiting on Day 1, which resolved on same day Highest dose to be used in Phase 2 trials is single I.V. loading dose of 20mg/kg Non-specific indicator of autoimmune disease present in up to 25% of healthy individuals: https://www.labcorp.com/assets-media/2785 Anti-double-stranded deoxyribonucleic acid antibodies are highly specific markers of systemic lupus erythematosus or SLE
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 require only one additional Phase 3 of similar design with more patients 300mg and 600mg S.C. Q2W dosing surpasses IC90 (87 µg/mL) and IC95 (149 µg/mL), respectively MaGic Trial: https://clinicaltrials.gov/study/NCT06282159 Highlights Design: 60 male and female subjects randomized to receive either DNTH103 or placebo for 13 weeks Inclusion: ≥18 years old with AChR antibody + gMG Dosing: 15 or 20mg/kg I.V. Loading Dose followed by 300mg or 600mg1 S.C. Q2W starting Day 7 Endpoints Primary: Safety Secondary: Efficacy (MG-ADL and QMG) Screen: Day -42 to -1 Day 0 Open-Label Extension: 52 Weeks DNTH103 300mg S.C. (n=20) DNTH103 600mg S.C. (n=20) Placebo (n=20) 12-Week S.C. Treatment Collect data for Safety, PK, PD, MG-ADL, QMG Loading Dose Randomization
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 surpasses IC90 (87 µg/mL) and IC95 (149 µg/mL), respectively MoMeNtum Trial: https://clinicaltrials.gov/study/NCT06537999 Highlights Design: 36 participants randomized to receive either DNTH103 or placebo for 17 weeks Inclusion: ≥18 years old with MMN who are immunoglobulin responsive and dependent Dosing: I.V. Loading Dose followed by 300mg or 600mg S.C. Q2W starting Day 7 Endpoints Primary: Safety Secondary: Efficacy (time to IVIg retreatment, time to relapse, grip strength and other muscle strength and motor function measurements) Screen & Ig Monitoring Day 0 Open-Label Extension: 52 Weeks DNTH103 300mg S.C. (n=12) DNTH103 600mg S.C. (n=12) Placebo (n=12) 17-Week S.C. Treatment Collect data for safety, PK, PD, time to IVIg retreatment, time to relapse, grip strength and other muscle strength and motor function measurements Loading Dose 1 Week Wait Before Randomization
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. Q2W N=64 Screen PART A: Up to 13-Week Open Label DNTH103 only PART B: 52-Week Pbo-controlled RCT CIDP diagnosis confirmed by an Independent CIDP Review Panel (ICRP) Open-Label Extension: 104 Weeks Loading Dose Day 0 Interim Responder Analysis N=40 DNTH103 300mg S.C. Q2W 300mg and 600mg S.C. Q2W dosing surpasses IC90 (87 µg/mL) and IC95 (149 µg/mL), respectively Highlights Design: All subjects receive DNTH103 in Part A for up to 13 weeks. Only responders randomized to Part B for 52 weeks Inclusion: ≥18 years old with confirmed CIDP, including SOC-refractory, SOC-stable or SOC-naïve Dosing: I.V. Loading Dose followed by 300mg S.C. Q2W in Part A; followed by 300mg or 600mg or Placebo in Part B Endpoints Part A: Response as measured as ≥1 point decrease (improvement) in adjusted INCAT score compared to Part A baseline Part B Primary: Efficacy (time to relapse) as measured as ≥1 point increase in adjusted INCAT Responders Randomized 1:1:1 to Part B Enrolling a broad patient population including SOC-refractory patients, in addition to SOC-stable and SOC-naïve patients All confirmed CIDP patients receive convenient 300mg S.C. Q2W dosing of DNTH103 in Part A Only responders from Part A randomized into the double-blind, placebo-controlled Part B
Corporate
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 outstanding2 2H Top-line Ph. 2 data Q4 Ph. 3 IND cleared Includes unaudited cash, cash equivalents and investments as of 9/30/24 Shares outstanding on a pro forma basis, which assumes the exercise of all outstanding pre-funded warrants https://argenx.com/news/2024/argenx-reports-third-quarter-2024-financial-results-and-provides-business-update.html https://www.sanofi.com/assets/dotcom/content-app/events/investor-presentation/2023/r-and-d-day-2023/Presentation.pdf#page=91 2H Top-line Ph. 2 data ‘26: Potential top-line Ph. 3 data and BLA submission4 for riliprubart in CIDP Q3 Initiated Ph. 2 trial Q4: Empasiprubart registrational study. initiation in MMN3 ‘25: Empasiprubart registrational study initiation in CIDP3 Ph. 1 data in 2023 showed potency and long half-life, and DNTH103 was generally well tolerated, allowing for 300mg/2mL Q2W S.C. dosing Initiated Ph. 2 trial in gMG in Q1’24 DNTH103 demonstrated greater affinity & PD potency as potential best-in-class aC1s inhibitor vs. riliprubart across multiple head-to-head in vitro experiments in Q2’24 Initiated Ph. 2 trial in MMN in Q3’24 IND cleared by FDA for Ph. 3 CIDP trial in Q4’24 Recent Accomplishments Interim Responder 2H
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 BOARD OF DIRECTORS Alison Lawton Chair of the Board Board Member, ProQR and X4, Prior Chair of Board, Magenta Tomas Kiselak Managing Member, Fairmount Anne McGeorge Board Member, The Oncology Institute, Board Member, Be the Match Lonnie Moulder Managing Member, Tellus BioVentures, Founder, CEO & Chairman, Zenas BioPharma Steven Romano, M.D. EVP, Chief Research & Development Officer, Silence Therapeutics, Inc. Paula Soteropoulos Venture Partner, 5AM Ventures Jonathan Violin, Ph.D. Venture Partner, Fairmount, Co-founder of Dianthus, Board Member, Astria Therapeutics, and former President/CEO of Viridian Therapeutics Marino Garcia President & CEO, Dianthus Select Auto-Immune Drugs Developed by Dianthus Team Jennifer Davis Ruff Head of Investor Relations & Corporate Affairs Jud Taylor Head of Technical Operations Ronny Hashmonay, M.D. Head of Medical Affairs Edward Carr Chief Accounting Officer Jeffrey Stavenhagen, Ph.D. Chief Scientific Officer Scott Nogi Head of Business Operations Polly Hanff Head of Quality Ryan Savitz Chief Financial Officer & Chief Business Officer Rivka Gluck, R.N. Head of Clinical Development, Operations Debra Segal Head of Regulatory Affairs
Appendix
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 DNTH103, as measured by decrease in muscle contraction fatigue Results confirm DNTH103 improved neurotransmission and muscle contraction https://pubmed.ncbi.nlm.nih.gov/34881241/, 2 - https://pubmed.ncbi.nlm.nih.gov/31846349/, 3 - https://pubmed.ncbi.nlm.nih.gov/30867827/ * Engineered using patent sequence AChR+ MG Patient Sera
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 profile of DNTH103 as a selective classical pathway inhibitor consistent with ENJAYMO, an approved C1S inhibitor without an FDA Boxed Warning or REMS Protection against infection is a critical function of the complement pathway DNTH103 selectively inhibits the classical pathway, leaving the alternative and lectin-activated defense pathways intact An in vitro assay measured antibody-dependent complement-mediated killing of N. meningitidis in the presence of DNTH103 and anti-C5 (ravulizumab*) In this assay, DNTH103 maintained bacterial killing, potentially leading to a decreased risk of infection vs. C5 inhibitors * Engineered using patent sequence
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
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 doses of DNTH103 as compared to baseline conduction velocity determined in sera from healthy volunteers (n=3) Results confirm DNTH103 completely restored conduction velocity across the axons of human motor neurons in the presence of autoantibodies from CIDP patient sera Rumsey, et al., Adv. Therap., 2022, 5(6): 2200030 Results for DNTH103 (1uM) include data from multiple conduction velocity recordings that exceed 1.0. For the purposes of this illustration, results are shown up to the baseline value 2