On June 23, 2020, Proactive hosted its One2One Virtual Forum, featuring several biotech company updates on their clinical programs. Presenting on behalf of Helix BioPharma (TSX:HBP.TO) was Dr. Heman Chao, CEO and Director of the company who presented the company’s drug pipeline, antibody conjugate technology, clinical milestones and financial position.
Helix BioPharma is a clinical stage biotechnology firm based in Ontario, Canada, focused on developing immuno-oncology cancer drugs. The company features the patented DOS47 therapeutic platform, designed to modulate the tumor microenvironment. Its lead clinical candidate is L-DOS47 which is targeting indications in lung and pancreatic cancer and secondary preclinical candidate is V-DOS47 which is targeting breast cancer.
Helix features a novel therapeutic approach to address the tumor microenvironment, specifically designed to reduce tumor acidity. Tumor acidity is the result of the hyperactive metabolism of the tumor during its growth, a phase which produces lactate. As cancers evolve, lactate production increases. Lactate was once dismissed as a byproduct of tumor metabolism; however, current thinking now considers lactate a secondary messenger that feeds back on itself, and also communicates with surrounding immune cells. Furthermore, cancer is complex, and single-agent approaches may struggle to control the disease. Recent success in immuno-oncology are still hindered by the acidic tumor microenvironment. By raising the tumor microenvironment pH, cancer therapies can be more effective, and the body’s own immune cells are less hindered. The DOS47 platform aims to counteract tumor acidification via a urease enzyme derivative, and can be used in conjunction with chemo- or immuno-therapies. Helix is the only company with drug in clinical development addressing the tumor microenvironment in this manner.
Currently, Helix has multiple indications in the pipeline: L-DOS47 as a monotherapy for NSCLC (Phase II), and in combination with various chemotherapy agents for the same indication. L-DOS47/doxorubicin for pancreatic cancer is currently in Phase Ib/II trials. L-DOS47 used with immunotherapy for NSCLC, and V-DOS47 for breast cancer are still in preclinical development.
As part of its presentation, Helix provided detail regarding some of its preclinical work in support of the mechanism of action of L-DOS47. Acidification of a murine pancreatic tumor was observed using CEST MRI. Thirty minutes after administration, tumor pH could be seen rising from an acidic 6-6.5 pH to almost neutral.
Exhibit I – CEST MRI imaging of murine advanced pancreatic tumor pH before and after L-DOS47 administration (1)
When used alone, L-DOS47 can suppress tumor growth, and when co-administered with Anti-PD-1 antibodies, tumor growth is almost completely controlled, confirming not only the function of L-DOS47, but also its potential as a therapeutic agent. Doxorubicin, a chemotherapy compound known to have varying efficacy with pH, was also tested in mice and found to have enhanced efficacy for tumor volume suppression when co-administered with L-DOS47.
L-DOS47 has also been evaluated in late-stage NSCLC patients who had exhausted therapeutic options as a monotherapy. In dose escalation, the patients become more stable, and in some cases, tumor size decreased, setting the foundation for advanced clinical studies. While the results did not meet the 30% threshold for partial response, data was directionally correct, and physician feedback was favorable.
Utility of chemo and immunotherapies, when used in tandem with L-DOS47, are enhanced. Recently released at ASCO 2020, Helix reported results from dose escalation on the use of L-DOS47 with pemetrexed and carboplatin in NSCLC (2). The 12 patients were late stage and chemo-naive. Patients were dosed in four cycles with the combination treatment. Those who did not progress following four cycles, and who did not suffer toxicity had the option to receive weekly doses of L-DOS47. Results were favorable with 75% of the 12 patients either remaining stable or achieving partial response (overall clinical benefit), again, laying the foundation for advanced clinical trials. Chemicals and proteins are sensitive to pH; single molecule compounds can have varying levels of protonation and proteins can be denatured and lose function, expensive and difficult to produce monoclonal antibodies included (3).
Exhibit II – Helix BioPharma Milestones and Capital Requirements (4)
Helix’ portfolio now has monotherapy data and data in US and Europe in combination with chemotherapeutics. It is now seeking partnership to evaluate L-DOS47 in combination with immunotherapy in the clinic. In the US, pancreatic studies are currently underway; Phase Ib is expected to complete by end of 2020, and Phase II will complete by end of 2021. If results are favorable, Helix can then prepare for a pivotal study in pancreatic cancer. Helix is currently undergoing the dose-escalating first stage of their Phase II NSCLC trial in Europe. Assuming results and medical committee oversight progress as planned, L-DOS47 will enter the randomized, second stage of the trial.
In terms of fundraising, Helix is currently in discussions to raise $15 million which should support the milestones outlined, excluding the pursued partnership for Phase II NSCLC in combination with immunotherapy. In addition, Helix expects to fully divest its European subsidiary, which may yield up to $1.7 million in funds. There will still be a licensing relationship between the two companies. With regard to equity presence in the US, Helix is targeting an up-list to the NASDAQ or other US exchange in late 2020.
On June 2, 2020, Helix provided an abstract from American Society of Clinical Oncology (ASCO) 2020 which reviews the Phase I dose escalation study of L-DOS47 with pemetrexed and carboplatin in non-small cell lung cancer (NSCLC). The purpose of the study was to identify the maximum tolerated dose (MTD) of L-DOS47 in combination with selected chemotherapeutics. Fourteen NSCLC patients were enrolled in the study who received increasing doses ranging from 0.59 to 12.0 μg/kg. No dose limiting toxicities (DLTs) were observed; however, half of patients experienced at least one treatment emergent adverse event (TEAE). 14.3% of patients experienced at least one Grade 3 or 4 drug-related toxicity. Twelve patients were evaluable for efficacy and five (41.7%) demonstrated a partial response, four (33.3%) presented stable disease and three (25%) experienced stable disease. A quarter of the evaluable population had progressive disease. The abstract concluded that L-DOS47 combined with chemotherapy is well tolerated with evidence of anti-tumor activity. We see the data as supportive of further work with chemotherapy and engaging a partner to advance the candidate in NSCLC.
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1. Source: Helix BioPharma Corporate Presentation June 2020
4. Source: Helix BioPharma Corporate Presentation June 2020