The product

Soluble Beta-Glucan (SBG®) is an active pharmaceutical ingredient with immunomodulatory properties derived from the cell wall of the yeast Saccharomyces cerevisiae. SBG is produced by a proprietary and patented method in compliance with Good Manufacturing Practice (GMP) in Biotec BetaGlucans’ production unit in Tromsø, Norway. The production and control of SBG® has been approved by the Norwegian Medicines Agency and is also been approved in accordance to ISO-13485 as a medical device ingredient.

SBG® is currently used as adjuvant in immunotherapy of cancer to strengthen the efficacy of an anti-GD2 neuroblastoma vaccine (NCT00911560) ongoing at Memorial Sloan Kettering Cancer Centre, NY, USA. The product has earlier been employed in clinical trials to potentiate cancer antibodies both in US and Norway (NCT00492167; NCT00533364; NCT00533728). SBG®, being a conserved pathogen associated molecular pattern (PAMP), has the ability to potentiate the effector mechanisms of white blood cells (e.g. macrophages and neutrophils) when recognising anti-body labelled cancer cells. The beta-glucan product would also enhance the immune response to antigens improving both the humoral and cellular immunity towards vaccines. A possible effect of beta-glucan on the tumor microenvironment (TME) has also been highlighted as a promising tool for improving immunetherapeutic strategies (Zhang et al. 2018, Frontiers in Immunology 9:341).

SBG® is also the bioactive ingredient in the wound healing product Woulgan® Gel for reactivating the healing process in stalled, and chronic wounds, where it acts primarily on white blood cells (especially macrophages).

Biotec Pharmacon has since the early 1990’s developed beta-1,3/1,6-glucans from yeast as a potent activator of innate immune functions for medicinal purposes. The soluble beta-glucan, SBG®, was originally developed as a classic vaccine adjuvant, although the product has mostly been employed in clinical trials where a general activation of innate immune cells has been the primary goal. A total of 14 clinical trials using SBG® have been performed ranging from treatment of oral mucositis, ulcers, wounds and burns (see woulgan.com), to investigating the adjuvant effect when combining SBG® with monoclonal antibodies (mAbs) and vaccine antigens in immunotherapy of cancer.

Soluble Beta-Glucan (SBG®) is a potent activator of innate immune cells, resulting in excellent adjuvant properties for strengthen immune responses together with cancer vaccines and monoclonal antibodies in immunotherapy of cancer. SBG® has been documented to have a very favourable toxicity profile and the safety of the product is fully documented. Since SBG® is administered orally (i.e. as a liquid solution), it can be combined with most mAbs and vaccine antigens to the patient concurrent to the i.v. /s.c. administration of mAb or vaccines. The combination therapy is protected by a number of granted and pending patents.


Background for the use of SBG® in immunotherapy of cancer

In 2002, the company initiated a co-operation with Memorial Sloan Kettering Cancer Centre (MSKCC) in New York, with the intention to investigate the potential of SBG® as adjuvant in immunotherapy of cancer. MSKCC had established reliable cancer models where it was possible to assess the efficacy of combining p.o. administered beta-glucans with i.v./s.c. administered monoclonal antibodies and cancer vaccines as the therapeutic agent. The preclinical cancer models clearly demonstrated the potential of combining SBG® treatment with the concurrent treatment with anti-cancer antibodies and vaccines.  The novelty of the MSKCC model was the oral administration of beta-glucan combined with  i.v. administered anti-cancer mAbs or sub cutaneous vaccine administration. The treatment effect of this combination gave birth to a number of new patents which are co-owned by MSKCC and Biotec Pharmacon. The concept of separating the route of administration of the two agents also gives a high degree of freedom for study design, dosage regimens, and clinical use.


SBG combined with anti-cancer antibodies

Mice were treated with a combination of anti-cancer antibody 3F8 (200 ug per day) i.v. twice weekly x 5 doses, and oral β-glucan (SBG) at 400 μg per day given per oral for a total of 18 days.
(US Pat 7,704,973)

The preclinical experience with SBG in combination with anti-cancer mAbs spurred the initiation of a phase I clinical trial in patients with stage 4 neuroblastoma (NCT00492167). In the study, MSKCC’s antibody against neuroblastoma (m3F8) was used at a fixed dosage in combination with stepwise increasing dosages of SBG (up to 200 mg/kg/day) in a total of 45 patients.  The combination was well tolerated even at the highest SBG dosages. The data was presented at Advances in Neuroblastoma Research (ANR) in 2008 (Modak et al. 2008).

123I-MIBG scans in a patient with refractory stage 4 neuroblastoma before (left) and after one cycle (right) of treatment with i.v. mAb 3F8 + p.o. SBG (80mg/kg/day)
123I-MIBG scans in a patient with refractory stage 4 neuroblastoma before (left) and after one cycle (right) of treatment with i.v. mAb 3F8 + p.o. SBG (80mg/kg/day).Modak et al 2008. Phase I study of combination of anti-gd2 antibody 3F8 and soluble yeast-derived (1→3), (1→6)-β-glucan (SBG) for resistant neuroblastoma. Poster C24 at ANR 2008 Chiba, Japan.

In parallel to the study at MSKCC, two separate phase I studies were performed investigating the combination of SBG with the anti-cancer antibodies Herceptin and Rituximab, in breast cancer (NCT00533364) and Non-Hodgkin’s lymphoma (NCT00533728) patients, respectively. Both studies concluded that the combination was well tolerated.


SBG combined with cancer vaccine

A model study at MSKCC demonstrated SBG administered per orally would also enhance the immune responses towards sub cutaneous administered vaccine antigens (Ragupathi et al. 4860-65). This observation combined with the knowledge that SBG could enhance the immune mechanisms eradicating tumor cells spurred the initiation of a clinical trial where SBG is combined with a bivalent vaccine against neuroblastoma (NCT00911560). The study is ongoing and aims to recruit a total of 185 patients by end of 2018. The first part of the study (phase I) has been published in Clinical Cancer Research concluding that the combination is safe, and could be used in outpatient clinic (Kushner et al. 2014, Clin Cancer Res 20:1375-1382).

Survival of patients treated with bivalent ganglioside vaccine in combination with SBG (40 mg/kg/day) for high-risk neuroblastoma. Relapse free survival (red) and overall survival (black) in 15 patients from start of vaccination (Kushner et al.).

Based on the encouraging initial results the study moved into phase II part, that by April 2018 had recruited almost 170 patients. The preliminary data for 84 patients from the study is presented at the 2018 Advances in Neuroblastoma Research (ANR) in San Francisco (Cheung et al 2018).

Patients treated under the neuroblastoma vaccine protocol since the initiation of the study in 2009.