IFx-2.0 / TuHURA Bio - LARVOL DELTA

pAc/Emm55 increases anti-melanoma immunity via TLR2 signaling in dendritic cells and improves checkpoint blockade efficacy. (PubMed, Front Immunol) - "Emm55 facilitates the TLR2-MyD88 pathway in DCs and subsequent IFN-γ production by OT-I CD8 T cells. Combining intratumoral IFx-Hu2.0 with PD-1 blockade improves tumor control, supporting clinical evaluation of this strategy as also suggested by the first-in-human clinical trial of IFx-Hu2.0."

Checkpoint inhibition • First-in-human • Journal • Gene Therapies • Melanoma • Oncology • Solid Tumor • CD8 • IFNG • ITGAX • MYD88 • TLR2 • TLR7

Currently Anticipated Milestones by Program: IFx-2.0 (Innate Immune Agonist) (PRNewswire) - "2H 2026: Expect to receive orphan drug designation in MCC; 1H2027: Expect preliminary results from IR study IFX-2.0 with Keytruda for deep seated MCC; 2H 2027: Expect to complete enrollment in the Phase 3 study of IFx-2.0."

Enrollment status • Orphan drug • P1 data • Merkel Cell Carcinoma

Mechanistic insights into IFx-Hu2.0 responses in the first human trial after prior anti-PD-1 therapy failure (AACR 2025) - "The expression of Emm55 in a B16 murine melanoma model induces a direct anti-tumor and abscopal effect, with antibodies to Emm55 detected in murine sera. Further research is needed to assess the role of these antibodies in anti-tumor immunity. Unique clones from TCRSeq and BCRSeq suggest that IFx-Hu2.0 may be a personalized vaccine."

First-in-human • IO biomarker • Melanoma • Oncology • Solid Tumor

Upcoming Targeted Milestones by Program (PRNewswire) - "IFx-2.0 (Innate immune agonist): 1H 2026: Anticipate Orphan Drug Designation for IFx-2.0 in MCC; 2H 2026: Anticipate preliminary data from the Phase1b/2a study of IFx-2.0 as an adjunctive therapy to Keytruda (pembrolizumab) in first line treatment for metastatic Merkel Cell Carcinoma of Unknown Primary Origin (MCCUP); 2H 2027: Anticipate topline results from the Phase 3 accelerated approval trial of IFx-2.0 as an adjunctive therapy to Keytruda (pembrolizumab) in first line treatment for advanced or metastatic MCC."

Orphan drug • P1/2 data • P3 data: top line • Merkel Cell Carcinoma

'Our current focus with IFx-2.0 is targeting completion of enrollment in our Phase 3 study of IFx-2.0 in combination with Keytruda for the first-line treatment of advanced or metastatic Merkel Cell Carcinoma.' (PRNewswire)

Enrollment status • Merkel Cell Carcinoma

TuHURA Biosciences received FDA Orphan Drug Designation for IFx-2.0 for the Treatment of Stage IIB to Stage IV Cutaneous Melanoma (PRNewswire) - "The ODD designation was based on data from the Company's previously completed Phase 1 study of IFx-2.0..."

Orphan drug • Cutaneous Melanoma

Upcoming Targeted Milestones by Program: IFx-2.0 (Innate immune agonist) (PRNewswire) - "(i) Q2 2026: Anticipate preliminary results from Phase 1b/2a clinical trial of IFx-2.0 as an adjunctive therapy to pembrolizumab in first line treatment for MCC of unknown primary origin (MCCUP); (ii) Q4 2026: Anticipate completion of enrollment in the randomized, placebo-controlled Phase 3 accelerated approval trial in first line treatment as adjunctive therapy to Keytruda in advanced or metastatic MCC; (iii) Q1 2027: Anticipate topline results from the Phase 3 accelerated approval trial."

Clinical data • Enrollment status • Merkel Cell Carcinoma

Placebo-Controlled Trial of IFx-Hu2.0 Followed By Pembrolizumab In Checkpoint Inhibitor Naïve Participants With Advanced Or Metastatic Merkel Cell Carcinoma (clinicaltrials.gov) - P2/3 | N=118 | Recruiting | Sponsor: TuHURA Biosciences, Inc. | Initiation date: Jun 2025 ➔ Oct 2025 | Not yet recruiting ➔ Recruiting

Checkpoint inhibition • Enrollment open • Trial initiation date • Merkel Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Solid Tumor

IFx-Hu2.0 As An Adjunctive Therapy To Pembrolizumab In Advanced Or Metastatic Merkel Cell Carcinoma (MCC) (clinicaltrials.gov) - P1 | N=9 | Recruiting | Sponsor: TuHURA Biosciences, Inc. | Not yet recruiting ➔ Recruiting | Initiation date: Apr 2025 ➔ Oct 2025

Checkpoint inhibition • Enrollment open • Trial initiation date • Merkel Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Solid Tumor

Upcoming Targeted Milestones by Program: IFx-2.0 (GlobeNewswire) - "(i) Year-End 2025: TuHURA anticipates providing an update on enrollment progress in its Phase 3 accelerated approval trial of IFx-2.0 as an adjunctive therapy to pembrolizumab in first line MCC; (ii) Q1 2026: Anticipated topline results from Phase 1b/2a clinical trial of IFx-2.0 as an adjunctive therapy to pembrolizumab in first line treatment for MCC of unknown primary origin (MCCUP); (iii) 2H 2026: Anticipated topline results from Phase 3 accelerated approval trial."

Clinical data • Enrollment status • Merkel Cell Carcinoma

TuHURA Biosciences Initiates Its Phase 3 Accelerated Approval Trial of IFx-2.0 as an Adjunctive Therapy to Keytruda (pembrolizumab) in First Line Treatment for Advanced or Metastatic Merkel Cell Carcinoma (PRNewswire) - "TuHURA Biosciences...announced the initiation of its Phase 3 accelerated approval trial of IFx-2.0, TuHURA's lead innate immune agonist, in patients with advanced or metastatic Merkel cell carcinoma (MCC)....The Company's Phase 3 accelerated approval trial of IFx-2.0, conducted under an SPA Agreement with the U.S. FDA, will evaluate IFx-2.0 as an adjunctive therapy administered weekly for three weeks concurrent with the approved dose and schedule for Keytruda compared to Keytruda plus placebo in the first line treatment for patients with advanced or metastatic MCC....The pivotal trial for IFx-2.0 is expected to enroll 118 participants across approximately 22 to 25 U.S. sites....The initiation of the Phase 3 trial represents the achievement of a milestone for the third tranche of funding under the Company's recently announced private placement, thereby trigging the purchase from the Company of an additional $2.23 million under the private placement financing."

Financing • Trial status • Merkel Cell Carcinoma

FDA Removes Partial Clinical Hold on TuHURA Biosciences' Phase 3 Accelerated Approval Trial for IFx-2.0 in Advanced or Metastatic Merkel Cell Carcinoma (Yahoo Finance) - "TuHURA Biosciences...announced that the FDA has removed the manufacturing-related partial clinical hold on the Company's Phase 3 accelerated approval trial for IFx-2.0, thereby allowing the trial to proceed as agreed to under the previously announced SPA Agreement with the FDA....'The removal of the partial clinical hold allows TuHURA to begin the trial's initiation and activation of clinical sites for the Phase 3 accelerated approval trial of IFx-2.0'..."

FDA event • Trial status • Merkel Cell Carcinoma

Multicenter, randomized, double-blinded, placebo-controlled trial of IFx-Hu2.0 (IFx) as adjunctive therapy with pembrolizumab (pembro) in checkpoint inhibitor (CPI)-naïve patients with advanced or metastatic Merkel cell carcinoma (MCC). (ASCO 2025) - "Primary and key secondary endpoints include objective response rate and progression-free survival respectively. Other secondary endpoints are safety, duration of response, and overall survival."

Checkpoint inhibition • Clinical • IO biomarker • Metastases • Merkel Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • CD14

TuHURA Biosciences Presents IFx-Hu2.0 Trial-in-Progress Poster at the 2025 American Society of Clinical Oncology Annual Meeting (PRNewswire) - "TuHURA Biosciences...announced that Moffitt Cancer Center presented a Trial in Progress poster of the Company's planned Phase 3 accelerated approval trial at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting on June 1, 2025....The Company's Phase 3 accelerated approval trial of adjunctive IFx-Hu2.0, to be conducted under a SPA agreement with the U.S. FDA, will evaluate IFx-Hu2.0 (0.1 mg) as an adjunctive therapy administered weekly for three weeks concurrent to pembrolizumab (200 mg) Q3W, compared to the same pembrolizumab regimen plus placebo. The pivotal trial is expected to enroll 118 CPI-naïve patients with advanced or metastatic MCC across approximately 22 to 25 U.S. sites."

Trial status • Merkel Cell Carcinoma

TuHURA Biosciences, Inc. Reports First Quarter 2025 Financial Results and Provides a Corporate Update (PRNewswire) - "Upcoming Anticipated Milestones by Program: IFx-Hu2.0: (i) Q2 2025: TuHURA anticipates the FDA's complete response letter lifting the partial clinical hold relating to completion of certain CMC requirements; (ii) Q2 2025: Initiation of Phase 3 accelerated approval trial in first line Merkel cell carcinoma."

FDA event • New P3 trial • Merkel Cell Carcinoma

TuHURA Biosciences, Inc. to Present at the 3rd Annual H.C. Wainwright BioConnect Conference (PRNewswire) - "TuHURA Biosciences, Inc...today announced that James A. Bianco, M.D., President and Chief Executive Officer of TuHURA, will present a company overview, including highlights of its IFx-Hu2.0 Phase 3 program, and its first-in-class bi-specific immune modulating Antibody drug, or peptide conjugates (ADCs, APCs) targeting Myeloid Derived Suppressor Cells (MDSCs), along with Kineta Inc's. VISTA inhibiting monoclonal antibody program, at the 3rd Annual H.C. Wainwright BioConnect Investor Conference at NASDAQ on Tuesday, May 20, 2025, at 2:30 PM ET."

Trial status • Merkel Cell Carcinoma

TuHURA Biosciences, Inc. Initiates Phase 1b/2a Study of IFx-Hu2.0 as an Adjunctive Therapy to Keytruda (pembrolizumab) in First Line Treatment for Metastatic Merkel Cell Carcinoma of Unknown Primary Origin (MCCUP) (PRNewswire) - "TuHURA...announced the initiation of its Phase 1b/2a trial of IFx-Hu2.0...in patients with MCCUP who would not be eligible for the Company's planned Phase 3 accelerated approval trial, which is targeted to begin enrollment later in Q2 2025...The Phase 1b/2a trial of IFx-Hu2.0 is...designed to assess the safety and feasibility of IFx-Hu2.0 as adjunctive therapy to pembrolizumab in adult patients with non-cutaneous MCC. The trial is designed to enroll a total of nine non-cutaneous MCC patients with either hepatic, pulmonary, or retroperitoneal lesions, enrolling three patients per lesion type (NCT06940440)...Data from the trial is anticipated by the end of Q4 2025 or early Q1 2026...TuHURA is also preparing to initiate...Phase 3 accelerated approval trial of IFx-2.0....The Company has reached agreement with U.S. Food and Drug Administration (FDA) on requirements for lifting a partial clinical hold on this trial and believes it will meet the requirements in Q2 2025."

P1/2 data • Trial status • Merkel Cell Carcinoma

IFx-Hu2.0 As An Adjunctive Therapy To Pembrolizumab In Advanced Or Metastatic Merkel Cell Carcinoma (MCC) (clinicaltrials.gov) - P1 | N=9 | Not yet recruiting | Sponsor: TuHURA Biosciences, Inc.

Checkpoint inhibition • New P1 trial • Merkel Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Solid Tumor

Placebo-Controlled Trial of IFx-Hu2.0 Followed By Pembrolizumab In Checkpoint Inhibitor Naïve Patients With Advanced Or Metastatic Merkel Cell Carcinoma (clinicaltrials.gov) - P2/3 | N=118 | Not yet recruiting | Sponsor: TuHURA Biosciences, Inc.

Checkpoint inhibition • New P2/3 trial • Merkel Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Solid Tumor

TuHURA Biosciences and Kineta Present Updated Results from…TuHURA's Mechanism of IFx-Hu2.0 Responses After Anti-PD-1 Therapy Failure in Advanced Melanoma at the American Association for Cancer Research Annual Meeting (PRNewswire) - "TuHURA also announced that the Markowitz Lab at Moffitt Cancer Center also presented a poster of TuHURA's IFx-Hu2.0 in patients with advanced treatment refractory Melanoma who, like patients in TuHURA's Phase 1b Merkel cell carcinoma trial, progressed while on CPI therapy. The data demonstrated that, among heavily pre-treated patients with advanced Melanoma who were resistant to anti-PD-1-based therapy, following IFx-Hu2.0, three of four patients achieved clinically meaningful, durable anti-tumor responses following re-administration of a CPI....'We look forward to that anticipated initiation of our Phase 3 accelerated approval trial in first line treatment of patients with advanced or metastatic Merkel cell carcinoma targeted for later this quarter'."

New P3 trial • P1 data • Melanoma • Merkel Cell Carcinoma

Immunotherapy With IFx-Hu2.0 Vaccine for Advanced Non-melanoma Skin Cancers (clinicaltrials.gov) - P1 | N=23 | Completed | Sponsor: TuHURA Biosciences, Inc. | Active, not recruiting ➔ Completed

Trial completion • Genetic Disorders • Merkel Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer

Immunotherapy With IFx-Hu2.0 Vaccine for Advanced Non-melanoma Skin Cancers (clinicaltrials.gov) - P1 | N=23 | Active, not recruiting | Sponsor: TuHURA Biosciences, Inc. | Trial completion date: Mar 2024 ➔ Aug 2024

Metastases • Trial completion date • Genetic Disorders • Merkel Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer

Kintara Therapeutics and TuHURA Biosciences Provide Update on Recent Corporate and Clinical Advancements and Outline Near Term Milestones (PRNewswire) - "Recent Clinical Advancements...Advanced enrollment, dosing and clinical site expansion in Kintara's open label 15-patient REM-001 study in cutaneous metastatic breast cancer (CMBC); As of June 26, 2024, four patients have been dosed in the open label 15-patient REM-001 study in CMBC; In addition to Memorial Sloan Kettering Cancer Center, Montefiore Medical Center, the University Hospital for Albert Einstein College of Medicine, will soon begin screening patients...Expected Near-term Milestones....Q4 2024: Complete enrollment and 8 week follow-up of 10 patients in the REM-001 study; 2H 2024: Commence TuHURA's Phase 3 trial for IFx-2.0 personalized cancer vaccine for advanced Merkel cell carcinoma under FDA's accelerated approval pathway."

Enrollment status • New P3 trial • Trial status • Breast Cancer • Merkel Cell Carcinoma • Oncology • Skin Cancer • Solid Tumor

Phase 1b trial of IFx-Hu2.0, a novel in situ cancer vaccine, in checkpoint inhibitor-resistant Merkel cell carcinoma (MCC) and cutaneous squamous cell carcinoma (cSCC). (ASCO 2024) - P1 | "IT IFx-Hu2.0 is safe and feasible to administer at weekly dosing repeated up to 3 weeks. An unplanned exploratory analysis revealed frequent (56%) and durable responses in advanced MCC to ICI re-challenge despite prior resistance to this class of drug, suggesting that IFx induced an immune priming effect. Preliminary biomarker analyses to investigate this phenomenon are ongoing and will be presented."

Checkpoint inhibition • IO biomarker • P1 data • Hepatology • Merkel Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer

TuHURA Biosciences and Kintara Therapeutics Announce Positive Results from Phase 1b Trial of IFx-2.0, a Novel Personalized Cancer Vaccine, in Checkpoint Inhibitor Resistant Advanced Merkel Cell Carcinoma (MCC) and Cutaneous Squamous Cell Carcinoma (cSCC) (PRNewswire) - P1b | N=23 | NCT04160065 | Sponsor: TuHURA Biosciences, Inc. | "TuHURA Biosciences...today announced positive results from the primary analysis of TuHURA's completed Phase 1b trial evaluating IFx-2.0 among patients with advanced or metastatic MCC or cSCC who exhibited primary resistance to immune checkpoint inhibitor (ICIs) therapy...Five (5) of these 7 patients progressed within 3.8 months while receiving single agent anti-PD(L)-1 therapy. IFx-2.0 was administered as the immediate post ICI therapy. Following IFx-2.0 treatment, patients were rechallenged with an anti-PD(L)-1 agent. Four (4) of the 5 patients (80%) achieved a durable objective response (CR, pCR, 2 PRs) lasting, on average, 25 months, with 2 responses ongoing at 19 and 23 months."

P1 data • Cutaneous Melanoma • Melanoma • Merkel Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma