On March 23rd, it was announced that BioLineRx Ltd. (NASDAQ/TASE: BLRX), a clinical-stage biopharmaceutical company focused on oncology and immunology, had acquired Agalimmune Ltd., a private UK-based company with an innovative, anti-cancer immunotherapy platform for a multi-million dollar upfront payment with potential access to substantial additional future payments based on development and commercial milestones.
Agalimmune uses an innovative approach to immuno-oncology first identified by Nobel Laureate Dr. Kary Mullis who had the idea to recruit anti-Gal antibodies, the most common antibody found in humans, to sites on tumours so that the body’s natural immune response is stimulated to attack the cancer. This approach holds the promise of not only killing the tumour cells at the site of injection, but also bringing on a longer-term anti-metastatic immune response. Agalimmune’s lead compound is AGI-134, a synthetic alpha-Gal immunotherapy in development for solid tumours. AGI-134 has completed numerous pre-clinical studies, demonstrating robust protection against the development of secondary tumours in a model of melanoma with only a single dose administered. Synergy has also been demonstrated in pre-clinical studies when AGI-134 is combined with a PD-1 immune checkpoint inhibitor, offering the potential to broaden the utility of such immunotherapies and improve the rate and duration of responses in multiple cancer types. AGI-134 is in near-clinical development and is expected to commence a first-in-man study in patients with solid tumours in the first half of 2018.
In March 2016, Horizon Discovery partnered with Centauri Therapeutics to form Avvinity Therapeutics (Avvinity), a joint venture established to explore the potential of a powerful and proprietary platform called Alphamers to discover and develop novel immuno-oncology therapeutics for the treatment of both solid tumours and leukaemias. Alphamers exploit the same anti alpha-Gal mechanism and promise key advantages over conventional antibody and antibody-drug conjugate molecules in immuno-oncology applications, including the ability to target cancers driven by both wild type ("normal") gene overexpression as well as mutant ("abnormal") gene overexpression, and by exhibiting a short half-life in the body yielding reduced toxicity and systemic side-effects.
Horizon's gene editing, immunology, oncology and drug discovery capabilities are being used to support Avvinity, which currently has multiple research-stage programmes underway. Updates will be provided as these programmes advance.
Dr. Darrin M. Disley, CEO, Horizon Discovery commented: “The acquisition of Agalimmune is another indication of the importance of immuno-oncology in the fight against cancer, a market currently worth £25 billion per year in 2015 and expected to grow to approximately £50 billion per year by 2020 (1). Given the demand from pharmaceutical companies for programmes in this area, and the acquisition of Agalimmune which uses a similar mechanism to re-directing the human immune system to target cancer to that of Avvinity, we feel that there is substantial opportunity to bring significant value creation to Horizon shareholders.”
Alphamer technology is based on chemically synthesized molecules that redirect naturally occurring antibodies in the human immune system to selected pathogens or cancer cells. One end of a molecule binds a cell-surface target on a pathogen or cancer cell using an aptamer, while the other end presents specific epitopes that attach to the circulating antibodies. The result of this redirection is cell death and subsequent recruitment of the T-Cell mediated pathways to clear the body of the pathogen or cancer cell.
Alphamers promise key advantages over conventional antibody and antibody-drug conjugate molecules in immuno-oncology applications, including the ability to target cancers driven by both wild type ("normal") gene overexpression as well as mutant ("abnormal") gene overexpression, and by exhibiting a short half-life in the body yielding reduced toxicity and systemic side-effects. Considerable investment has been made in the Alphamer technology over the past four years and its ability to engage the immune system to destroy bacteria has been confirmed (3).
References and notes:
2. Platform technologies based around alternative immuno-oncology approaches have secured high valuations once early positive results in clinical trials have been achieved: Amgen's 2012 acquisition of Micromet valued Micromet at $1.16b, and in 2013, Spirogen was acquired by AstraZeneca for up to $440m.
3. Retargeting pre-existing human antibodies to a bacterial pathogen with an alpha-Gal conjugated aptamer. Kristian SA, Hwang JH, Hall B, Leire E, Iacomini J, Old R, Galili U, Roberts C, Mullis KB, Westby M, Nizet V. J Mol Med (Berl). 2015 Jun;93(6):619-31