DiaPep277 / Evotec, Amgen - LARVOL DELTA

Plasmodium falciparum FIKK9.1 is a monomeric serine-threonine protein kinase with features to exploit as a drug target. (PubMed, Chem Biol Drug Des) - "Correlation analysis of peptides from the combinatorial library concluded that peptide P277 (MFDFHYTLGPMWGTL) was fitting nicely into the binding pocket...Interestingly, FIKK9.1 is phosphorylating spectrin, ankyrin, and band-3 from RBC cytoskeleton. Our study highlights the structural and biochemical features of FIKK9.1 to exploit it as a drug target."

Journal • Spectrin

Evotec: R & D Day (Evotec) - P2, N=NA; "DiaPep277-Phase II results"; "C-peptide levels significantly declined in placebo group"; "C-peptide levels were maintained in DiaPep277 group"; "Need for exogenous insulin higher in placebo group; "HbA1c levels around 7% in both groups"; "T cell reactivity shifted towards Th2 cytokine phenotype in DiaPep277 group"

P2 data • Diabetes

Subgroup analysis of DIA-AID 1, an immune intervention phase III study in newly diagnosed type 1 diabetes patients (ADA 2013) - Presentation time: Sun 6/23 5:45 PM – 6:00 PM; Abstract #249-OR; P3, DIA-AID 1 (NCT00615264); “In 164 patients…the treatment effect was 34.5% (p=0.009) compared to 7.6% in patients randomized with baseline insulin > 0.35 IU/kg/day (144 patients).Among 152 patients older than 27 years the treatment effect was 44.4% (p=0.009).In 99 patients from Northern European countries with high prevalence of T1D, the treatment effect was 34% (p=0.046).In 142 patients with moderate and high risk HLA genotype the treatment effect was 35.4% (p=0.017).”

P3 data • Diabetes

Evaluation of long-term treatment effect in a type 1 diabetes intervention trial: Differences after stimulation with glucagon or a mixed meal (Diabetes Care) - P3, N=343; NCT00615264; Sponsor: Andromeda Biotech; “The absolute AUC values obtained at any single time point by the two tests were well correlated in both data sets (r = 0.74-0.9). However, the correlations between the AUC were much weaker (r = 0.39-0.58).”

P3 data • Diabetes

Andromeda announces phase III clinical study with DiaPep277, a novel immunotherapeutic agent for type 1 diabetes, met primary endpoint (Market Watch) - P3, N=457; Andromeda Biotech Ltd. announces initial results from a pivotal P3 clinical study; The results show that study has met its primary endpoint, defined as change from baseline in C-peptide levels at end of the study; The study also achieved a key secondary endpoint, showing that a greater proportion of DiaPep277 treated pts maintained good diabetic control compared to the pbo, measured by HbA1c levels equal or less than 7% at the end of the study (45.5% versus 35.7%, p=0.035)

P3 results • Diabetes

Andromeda Biotech successfully completes patient recruitment in phase 3 confirmatory trial for its lead drug, DiaPep277 for type 1 diabetes (Andromeda) - Andromeda Biotech has completed patient recruitment in its DIA-AID 2, a confirmatory P3 clinical trial using DiaPep277 for the treatment of type 1 diabetes; Anticipated P3 data in Q4 2014

Anticipated P3 data • Trial completion date • Diabetes

Andromeda announces the results of an extension to its phase III study (Andromeda) - P3, N=43; NCT00644501; Sponsor: Andromeda; "...announces the results from an Extension Study to its Phase III Clinical trial in type 1 diabetes patients...50% were in the group treated for four years compared to 28.6% in the group who were treated for two years and maintained HbA1c ≤ 7% at the end of the study. 37% versus 13% were in partial remission (HbA1c ≤ 7% and insulin daily dose ≤ 0.5 U/Kg).

P3 data • Diabetes

Long term safety and efficacy of DiaPep277- initial results of an extension study to DIA-AID 1 (EASD 2013) - Presentation time: Wed, Sep 25, 1:45 PM; Abstract # 560; P3, N=47; NCT00644501; Sponsor: Andromeda Biotech; “A higher proportion of patients who were treated for 4 years with DiaPep277® maintained fasting C-peptide ≥ 0.2 nmol/l at the end of the 2-year extension study, 42% compared to only 17% of the Placebo -DiaPep277® treated patients... maintained target HbA1c ≤ 7% at the end of the extension study, 59% vs 27% of the Placebo - DiaPep277® treated patients... full results of this study will be available by the end of 2013.”

Anticipated P3 data • P3 data: top line • Diabetes

Long term safety and efficacy of DiaPep277 - Results of an extension study to DIA-AID 1 (ADA 2013) - Presentation time: Sun 6/23 4:45 PM – 5:00 PM; Abstract #245-OR; P3, N=32; NCT00644501; “The proportion of patients who maintained fasting C-peptide ≥ 0.2 nmol/l at the end of the 2-year extension study was higher in the DiaPep277®... than in the Placebo - DiaPep277®treated arm, 42% vs 17%, respectively...The full results of this study will be available by the end of 2013.”

Anticipated P3 data • P3 data • Diabetes

Subgroup analysis of DIA-AID 1, an immune intervention phase 3 study in newly diagnosed type 1 diabetes patients (EASD 2013) - Presentation time: Wed, Sep 25, 1:45 PM; Abstract # 559; P3, N=557; NCT00615264; Sponsor: Andromeda Biotech; “...the treatment effect was 34.5% (p=0.009) compared to 7.6% in patients randomized with baseline insulin > 0.35 IU/kg/day (144 patients). Among 152 patients older than 27 years, the treatment effect was 44.4% (p=0.009). In 99 patients from Northern European countries with high prevalence of T1D, the treatment effect was 34% (p=0.046). In 142 patients with moderate and high risk HLA genotype, the treatment effect was 35.4% (p=0.017).”

P3 data • Diabetes

Third quarter earnings briefs: Lilly, Bristol, Shire, Biomarin, Alexion (Pink Sheet - Informa) - “A read-out from a second Phase III study is expected at the end of 2014, and launch might be possible in 2016”

Anticipated launch • Anticipated P3 data • Diabetes

Andromeda announces FDA orphan drug designation for DiaPep277 for the treatment of type 1 diabetes with residual beta cell function (Market Watch) - Andromeda Biotech today announced that the US FDA has granted Orphan Drug designation for DiaPep277 for the treatment of type 1 diabetes patients with residual beta cell function

Orphan drug • Diabetes

C-Peptide response and HLA genotypes in subjects with recent-onset type 1 diabetes after immunotherapy with DiaPep277: an exploratory study (Diabetes) - P=NA, N=146; DiaPep277 treated adults with low risk genotype had higher maximal & AUC C-peptide versus pbo at 12 months (p<0.01, & p<0.05, respectively); In moderate risk genotype group, Δmaximal & AUC C-peptide values were higher in DiaPep277-treated versus pbo treated patients (p<0.01 & p<0.05, respectively)

Biomarker data • Diabetes

The safety and efficacy of administrating DiaPep277 vaccination in type 1 diabetes patients (clinicaltrials.gov) - P1/2, N=20; Not yet recruiting; New P1/2 trial.

New P1/2 trial • Diabetes