ADAPTIVE AND INNATE IMMUNE RESPONSES
TRIGGERED TO NEUTRALIZE GASTRIN HORMONES
AS A THERAPY FOR GI CANCERS



TYG100
TYG oncologys first product candidate, TYG100, is a reversible cancer immunotherapy (RCI), for treatment of gastroenterological cancers such as pancreatic, stomach and colon cancer. TYG100 contains G17 (little gastrin) as tumour associated autoantigen.

Over $230M has been invested. Over 1100 patients have participated in clinical trials with no serious adverse effects to prove that hormone neutralization therapy is efficacious. Phase-III
*) clinical studies of the earlier drug candidate (G17DT, a therapeutic vaccine developed by Aphton Inc.) aiming at gastrin neutralization, demonstrated survival benefit (P<0.003) with good quality of life in responding patients. G17DT clinical trial design populations were minimal and immune-responder rates were statistically incomplete to justify regulatory approval.

A recent study in non human primates with TYG100 shows that TYG100 is the superior successor of G17DT. TYG100 promises to achieve > 100 fold higher anti-G17 IgG titres in almost 100% of the patients, thereby enabling an early regulatory approval pathway with a pivotal Phase II trial.

*) An International Multicenter Randomized Controlled Trial of G17DT in Patients With PDAC”, Gilliam A.D. et al, Pancreas 2011 www.pancreasjournal.com

MODE OF ACTION

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Step 1: Tumour cells produce autocrine growth factor “G17 “ -> relevant part of G17 is used as immunogen in TYG100
Step 2: TYG100 is recognized by auto-antigen specific B cell and binds to CD32b (low affinity)
and G17 specific B cell receptor (low affinity) -> increased avidity -> stable binding of TYG100
Step 3a: TYG100 is actively internalized; in the endosome TLR9 is triggered
Step 3b: Responsive G17 specific B cell presents TYG100 derived T cell epitopes on class II molecules and receives help from TYG100 specific T helper cells.
Step 4: Activated G17 specific B cell becomes plasma cell/blast and produces large amounts of G17 specific IgG antibodies
Step 5: G17 specific IgG antibodies prevent G17 to bind to CCK-2 receptor and tumour cells are deprived of their growth factor -> tumour cells die
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