L-DOS47 / Helix BioPharma - LARVOL DELTA

Helix BioPharma Corp. Announces Fiscal 2025 Year-End Results (The Newswire) - "Research and development expenditures for the year ended July 31, 2025, when compared to the year ended July 31, 2024, decreased by $2,419,000 or 40%. The change in spending during the year was the net effect of the conclusion of the Phase Ib/II study in metastatic pancreatic adenocarcinoma (LDOS006), collaborative research activities carried out by third parties on behalf of the Company, and stock-based compensation expenses based on the timing of the vesting of stock options issued to employees and consultants associated with research activities in the quarters ended July 31, 2025 and 2024."

Commercial • Pancreatic Ductal Adenocarcinoma

Helix BioPharma to Present Clinical Trial... (City Buzz) - "The company will highlight preparations for a Phase Ib/Randomized Phase II study of L-DOS47 combined with pembrolizumab for first-line non-small cell lung cancer treatment..."

Clinical • Non Small Cell Lung Cancer

Safety of unconventional antibody-drug conjugate L-DOS47 in a phase I/II monotherapy study targeting advanced NSCLC. (PubMed, Front Oncol) - P1/2 | "Screening for CEACAM6 expression may select patients who are more likely to derive benefit from L-DOS47. https://www.clinicaltrialsregister.eu/ctr-search/search; EudraCT Identifier: 2010-020729-42 (May 6, 2010)."

Journal • Monotherapy • P1/2 data • Embryonal Tumor • Lung Cancer • Metabolic Disorders • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Solid Tumor • CEACAM5 • CEACAM6

Helix Biopharma Corp. Announces Publication in Frontiers in Oncology on the Effects of L-DOS47 as Monotherapy in NSCLC (The Newswire) - "The Phase I/II open-label study demonstrated that L-DOS47 was well tolerated at doses up to 13.55 µg/kg. While no complete or partial responses were observed, post-hoc exploratory analyses in Phase I revealed that patients receiving higher doses experienced a statistically significant extension in progression-free survival (PFS), with median PFS reaching 4.1 months (approximately 16 weeks) in the highest dosing quartile (P=0.0203). This finding is particularly notable given that over 90% of these patients had received two or more prior lines of therapy."

P1/2 data • Non Small Cell Lung Cancer

L-DOS47 Plus Doxorubicin in Advanced Pancreatic Cancer (clinicaltrials.gov) - P1/2 | N=28 | Terminated | Sponsor: Helix BioPharma Corporation | Active, not recruiting ➔ Terminated; The primary reason for early termination was budget constraint.

Trial termination • Oncology • Pancreatic Cancer • Solid Tumor

Helix Biopharma Corp. Announces Upcoming Poster Presentation at the 20th European Molecular Imaging Meeting in Bilbao, Spain (Helix BioPharma) - "The study demonstrated that L-DOS47 effectively neutralizes the acidic tumor microenvironment (TME) in new CEACAM6-expressing solid tumors, a critical factor in tumor progression and immune evasion. In head and neck cancer and colon adenocarcinoma models, treatment with L-DOS47 raised tumor pH levels within 24 hours with a transient but measurable effect lasting up to 48 hours, effectively neutralizing acidity that fuels tumor growth. MRI scans and tissue analysis also revealed signs of tumor necrosis, underscoring L-DOS47’s impact on tumor viability. Importantly, the study confirmed that L-DOS47 precisely targets CEACAM6-expressing tumors while being safely cleared from the body."

Preclinical • Colon Adenocarcinoma • Head and Neck Cancer

Helix Biopharma Corp. Announces Issuance of U.S. Patent (Helix BioPharma Press Release) - "Helix BioPharma Corp...is pleased to announce the issuance of U.S. Patent No. 11931422. U.S. Patent No. 11931422, entitled ‘Antibody-Urease Conjugates for Therapeutic Purposes’, relates to Helix’ first-in-class antibody-drug conjugate (ADC) platform, L-DOS47, and the optimization of conjugation ratios for a proprietary antibody that precisely binds to tumor cells expressing high levels of CEACAM6, conjugated to urease, an enzyme capable of alkalizing the acidic tumor microenvironment (TME)."

Patent • Oncology

Helix Biopharma Corp. Attends World ADC San Diego (Helix BioPharma Press Release) - "Helix BioPharma Corp...is pleased to announce that the Company attended the 15th World ADC San Diego from 4–7 November 2024, the world's leading and longest-standing forum on antibody-drug conjugates (ADCs)....Helix was represented this year by its Medical Adviser, Haematologist-Oncologist and seasoned Pharma executive, Thomas Mehrling, to keep abreast of emerging trends and breakthroughs in the field, as the Company advances its development of L-DOS47, Helix’ first-in-class enzyme-antibody-drug conjugate platform technology."

Clinical • Non Small Cell Lung Cancer

L-DOS47 Plus Doxorubicin in Advanced Pancreatic Cancer (clinicaltrials.gov) - P1/2 | N=28 | Active, not recruiting | Sponsor: Helix BioPharma Corporation | Recruiting ➔ Active, not recruiting | N=20 ➔ 28 | Trial completion date: Aug 2025 ➔ Nov 2024

Enrollment change • Enrollment closed • Metastases • Trial completion date • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

A Dose Escalation Study of L-DOS47 in Recurrent or Metastatic Non-Squamous NSCLC (clinicaltrials.gov) - P1 | N=14 | Terminated | Sponsor: Helix BioPharma Corporation | Completed ➔ Terminated; Slow enrolment - standard of care evolved over the duration of the study such that treatment regimen employed in the study was no longer current standard of care for first line resulting in recruitment challenges.

Combination therapy • Metastases • Trial termination • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR

L-DOS47 Elevates Pancreatic Cancer Tumor pH and Enhances Response to Immunotherapy. (PubMed, Biomedicines) - "Using chemical exchange saturation transfer-magnetic resonance imaging (CEST-MRI) to measure the tumor extracellular pH (pHe), we confirmed that L-DOS47 raises the tumor pHe from 4 h to 96 h post injection in acidic tumors (average increase of 0.13 units). Additional studies showed that combining L-DOS47 with anti-PD1 significantly increases the efficacy of the anti-PD1 monotherapy, reducing tumor growth for up to 4 weeks."

Journal • Gastrointestinal Cancer • Gastrointestinal Disorder • Hepatology • Metabolic Disorders • Oncology • Pancreatic Cancer • Solid Tumor • CEACAM6

L-DOS47 Plus Doxorubicin in Advanced Pancreatic Cancer (clinicaltrials.gov) - P1/2 | N=20 | Recruiting | Sponsor: Helix BioPharma Corporation | Trial completion date: Aug 2023 ➔ Aug 2025 | Trial primary completion date: Aug 2023 ➔ Aug 2024

Metastases • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

Neutralizing acidosis with L-DOS47 urease immunoconjugate enhances responses to anti-PD1 checkpoint blockade in a preclinical orthotopic model of pancreatic adenocarcinoma. (AACR-NCI-EORTC 2023) - No abstract available

Checkpoint block • Checkpoint inhibition • Preclinical • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer

A Phase I, Open-Label, Dose Escalation Study of L-DOS47 in Combination with Pemetrexed/Carboplatin in Patients with Stage IV Recurrent or Metastatic Non-Squamous Non-Small Cell Lung Cancer (JTO Clin Res Rep) - P1 | N=14 | NCT02309892 | Sponsor: Helix BioPharma Corporation | "No dose-limiting toxicities were reported so the maximum tolerated dose was not reached. The objective response rate was 41.7% with a median duration of response of 187 days. Clinical benefit was observed in 75.0% of patients. After the first dose L-DOS47 systemic exposure increased in a generally dose-proportional manner but decreased substantially with repeat dosing. Anti-L-DOS47 antibodies (ADA) were detectable in 13/14 patients by Cycle 2 with titers typically increasing with continued treatment....L-DOS47 combined with standard pemetrexed/carboplatin chemotherapy is well tolerated in patients with recurrent or metastatic non-squamous NSCLC at doses up to 9.0 μg/kg."

P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Targeting acidosis to improve immunotherapy in a pancreatic ductal adenocarcinoma model (AACR-NCI-EORTC 2022) - "In this study, we test L-DOS47, a targeted urease immunoconjugate designed to directly neutralize tumor acidity that has been shown to be well-tolerated in phase I/IIa trials... This study shows that neutralizing acidic tumor pH strengthens the response to immune checkpoint blockade in the PDAC model. No"

Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CEACAM5 • CEACAM6

A Phase 1, Open-Label, Dose-Escalation Study of L-DOS47 in Combination With Pemetrexed Plus Carboplatin in Patients With Stage IV Recurrent or Metastatic Nonsquamous NSCLC. (PubMed, JTO Clin Res Rep) - "There was an apparent association between best overall response rate and highest anti-L-DOS47 antibody titer measured. L-DOS47 combined with standard pemetrexed and carboplatin chemotherapy is well tolerated in patients with recurrent or metastatic nonsquamous NSCLC at doses up to 9.0 μg/kg."

Combination therapy • Journal • P1 data • Hematological Disorders • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CEACAM6

L-DOS47 Plus Doxorubicin in Advanced Pancreatic Cancer (clinicaltrials.gov) - P1/2 | N=20 | Recruiting | Sponsor: Helix BioPharma Corporation | Trial completion date: Oct 2021 ➔ Aug 2023 | Trial primary completion date: Oct 2021 ➔ Aug 2023

Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

[VIRTUAL] Phase I dose escalation study of immunoconjugate L-DOS47 in combination with pemetrexed/carboplatin in non-squamous non-small cell lung cancer (NSCLC) patients. (ASCO 2020) - "L-DOS47, in combination with pemetrexed/carboplatin, appears to be well tolerated with promising anti-tumor activity against non-squamous NSCLC. Research Funding: Helix BioPharma Corp."

Clinical • Combination therapy • P1 data • Lung Adenocarcinoma • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

A Study of L-DOS47 in Combination With Vinorelbine/Cisplatin in Lung Adenocarcinoma (clinicaltrials.gov) - P2; N=9; Terminated; Sponsor: Helix BioPharma Corporation; N=136 ➔ 9; Suspended ➔ Terminated; Study was halted at this time due to other budgetary priorities.

Clinical • Combination therapy • Enrollment change • Trial termination • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Helix BioPharma Corp. Announces Fiscal Third Quarter 2021 Results (Yahoo Finance) - "Clinical development: (i) Phase I combination therapy study in lung cancer (LDOS001): Final clinical study report will be completed September 2021; (ii) Phase II combination therapy study in lung cancer (LDOS003): The Company previously announced that it would not be advancing the randomized portion of this study without third-party partner funding. To date, no third-party partner has been identified; (iii) L-DOS47 immunotherapy chemo combination study in lung cancer: The Company plans to submit an Investigational New Drug application by December 2021."

IND • P1 data • Trial status • Lung Cancer • Non Small Cell Lung Cancer • Oncology

A Study of L-DOS47 in Combination With Vinorelbine/Cisplatin in Lung Adenocarcinoma (clinicaltrials.gov) - P2; N=136; Suspended; Sponsor: Helix BioPharma Corporation; Recruiting ➔ Suspended

Clinical • Combination therapy • Trial suspension • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Helix Biopharma Corp. Announces Fiscal 2021 First Quarter Results (Yahoo Finance) - "At present, the only clinical program enrolling patients is the Company's U.S. Phase Ib/II LDOS006 study (L-DOS47 in combination with doxorubicin) in the treatment of patients with metastatic pancreatic cancer...Due to slower enrolment related to challenges resulting from COVID-19 pandemic measures, an additional two sites are engaged in study start-up activities, with plans to be open for patient recruitment in the first calendar quarter of fiscal 2021. A protocol amendment is also planned for submission to the U.S. Food and Drug Administration by the end of the month. The Company is working through the process of completing the anti-drug antibody assays for LDOS001 (U.S. Phase I L-DOS47 in combination with pemetrexed and carboplatin for lung cancer) with the goal of finalizing the clinical study report by April 2021..."

Clinical protocol • Trial status • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer

Targeting urease to human VEGFR2 elicits antitumor activity in triple-negative breast cancer models (AACR 2018) - "...The first, L-DOS47, is currently in clinical testing for non-small cell lung cancer... Our data show successful targeting of the DOS47 platform to human VEGFR2 expressed on tumor cells. Our in vivo data indicate that the antitumor activity of V21-DOS47 is enhanced in immunocompetent mice, which suggests that the immune system is a significant component of the antitumor activity of the V21-DOS47 immunoconjugate."

IO Biomarker • Preclinical • Non Small Cell Lung Cancer • Triple Negative Breast Cancer

L-DOS47: Completion of enrollment of P1b portion of P1b/2 trial (NCT04203641) for pancreatic cancer in Q2 2021 (Helix BioPharma) - Annual Report 2020: Initiation of P2 portion of P1b/2 trial for pancreatic cancer in November 2021

Enrollment status • Trial status • Oncology • Pancreatic Cancer

L-DOS47: Initiation of P3 trial for pancreatic cancer in 2022 (Helix BioPharma) - Annual Report 2020

New P3 trial • Oncology • Pancreatic Cancer