SGX942 Reduces the Duration of Severe Oral Mucositis in Head and Neck Cancer

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1 Reduces the Duration of Severe Oral Mucositis in Head and Neck Cancer Oreola Donini*, PhD, Chief Scientific Officer, Soligenix, Inc. Richard Straube*, MSc, MD, Chief Medical Officer, Soligenix Inc. Multinational Association for Supportive Care in Cancer Conference, 216 June 25, 216 *Conflict of Interest Statement: OD and RS receive compensation from Soligenix, Inc., and hold equity in Soligenix, Inc; OD is a co-inventor of. Company Name Honoraria/ Expenses Consulting/ Advisory Board Funded Research Royalties/ Patent Stock Options Ownership/ Equity Position Employee Other (please specify) Soligenix, Inc. x OD OD/RS OD/RS

2 : An Innate Defense Regulator PAMPs DAMPs IL1ra TNFα TLRs NODs p62 C/EBP1 etc IDRs () Selective Effector Cell Recruitment Pathogen Killing & Clearance Controlled Inflammation Wound debridement & healing Yu et al. JBC 29; 284(52):

3 Pathobiology of Mucositis Innate Defense Regulator: impacts all stages of mucositis initiation and progression Ref: S. Sonis 24 Active in nonclinical models of chemotherapy and radiation induced mucositis 3

4 Dose Selection Activity in oral mucositis (OM) in preclinical models at human equivalent dose of 1-2 mg/kg o Higher dose levels could not be assessed in rodents Anti-inflammatory markers indicated 1-2 mg/kg as the most effective dose in nonclinical and phase 1 studies IL-1Ra (pg/ml) Peak IL-1ra NHP # 11 NHP # 151 FOLD CHANGE IL-1R a/il-1β R atio 1 hr Timepoint p<.1 FOLD CHANGE TN FR II / TN Fα R atio 1 hr Timepoint p< HED: Placebo Low High Dose(mg/kg) PRIMATES PHASE 1 m g/kg m g/kg Placebo Low High m g/kg m g/kg North et al. J Biotech 216; 226:

5 Phase 2 Study Design Enrolled 111 head and neck cancer (HNC) patients planned to receive at least 55 Gy radiation and either weekly (3-4 mg/m 2 ) or every 3 rd week (8-1 mg/m 2 ) cisplatin o 96 patients received at least 55 Gy irradiation and constituted the primary mitt analysis population Dose escalating: Placebo, 1.5, 3. or 6. mg/kg administered twice weekly o 3. mg/kg included as a safety step only; not used for efficacy analysis Key efficacy endpoints: incidence and/or duration of severe OM Key safety endpoints: AEs, SAEs, lab results 5

6 Clinically Meaningful Results 5% decrease in duration of severe (WHO 3) OM Reduced infection rates Does not protect tumor ( complete resolution favored 1.5 mg/kg group) %Patients W ith at Least 1 Non-Fungal Infection %Non-Fungal Infection Placebo 1.5mg/kg 6.mg/kg Duration WHO 3 M edian ± 95%CI (Days) % Patients w ith W H O 3 at IF U Duration Severe OM 18 days Placebo N=38 p=.99 9 days 1.5mg/kg N=36 %Unresolved OM 22 days 6.mg/kg N=19 Placebo 1.5mg/kg 6.mg/kg 6

7 More Disease = Bigger Effect Size Subjects with higher incidence of OM experienced more benefit from o Reduced duration of ulcerative (WHO 2) OM also observed Duration Severe OM: Chemo Every 3 rd Week p=.4 Duration Ulcerative OM: Chemo Every 3 rd Week p=.99 Duration WHO 3 M edian ± 95%CI (Days) days 17 days 1 days Upper 95% CI not defined; Lower 95% CI = days 51 days 53 days Upper 95% CI not defined; Lower 95% CI = 14 Placebo Placebo 1.5mg/kg 6.mg/kg 1.5mg/kg 6.mg/kg N=22 N=24 N=1 7

8 Effective Dose = 1.5 mg/kg Endpoint 1.5 mg/kg 6. mg/kg mitt: Duration of SOM mitt: AUC of SOM mitt: Incidence mitt: Residual 1 m q3wk: Duration of SOM q3wk: AUC of SOM q3wk: Incidence of SOM mitt: Nonfungal infections mitt: Complete tumor response = no better than placebo = + trend = p<.1 = p<.5 8

9 Safety was well-tolerated in HNC patients undergoing chemoradiation therapy o No differences in the nature or severity of AEs and SAEs between treatment groups o No significant shifts in laboratory values o No impact on tumor resolution Consistent with 84-subject Phase 1 study in healthy volunteers % Complete Tumor Resolution at 1 month post EOT Incidence of "Complete" Tumor Resolution Placebo 1.5 m g/kg 6. m g/kg 9

10 Conclusions A non-linear dose response curve was observed, consistent with Phase 1 clinical and nonclinical studies o (1.5 mg/kg) decreased SOM 5% and 67% in patients at highest risk for SOM o (6. mg/kg) was less effective treating OM Achieved all study objectives: Showed safety in a sick patient population Identified most appropriate clinical endpoint Confirmed effective dose of Determined clinical effect size of Characterized patient population Determined that nonclinical biology translates to human setting Decreased duration OM Decreased incidence infection No detrimental impact on tumor control Results support further clinical study of in OM in HNC 1

11 National Institute of Dental and Craniofacial Research Phase 1 SBIR grant Medical Advisory Board: Dr. Steve Sonis, Dr. Dorothy Keefe, Dr. Mark Schubert Clinical Sites: Acknowledgments University of Kentucky (Dr. M. Kudrimoti) Gibbs Cancer Center, Spartanburg Regional Hospital (Dr. A. Curtis) Veteran s Affairs Long Beach Hospital (Dr. S. Azawi) University of Michigan Health System (Dr. F. Worden) Willis-Knighton Cancer Center (Dr. S. Katz) Washington University (Dr. D. Adkins) Wake Forest Health Sciences Medical Center (Dr. M. Bonomi) and IDR-OM-1 Study Group 11

Cellceutix Corporation Beverly, MA USA Abstract 2969; Presentation 0195; Hall J, 4:00pm. April 27, 2015

ECCMID 2015 Copenhagen, Denmark 25 28 April 2015 Cellceutix Corporation Beverly, MA USA www.cellceutix.com A Randomized, Double-Blind Study Comparing Single-Dose and Short-Course Brilacidin to Daptomycin