Soligenix, Inc. · NASDAQ:SNGX
Soligenix — Technical Presentation (December 2016)
61 slides from Soligenix's technical presentation, Dec 16, 2016
Slide 1: Investor Webcast: Innate Defense Regulators, Oral Mucositis and SGX942 Phase 2 Results
((SOLIGENIX Investor Webcast Innate Defense Regulators, Oral Mucositis and SGX942 (Dusquetide) Phase 2 Clinical Results ... Rising to the Challenges of Rare Disease Treatment NASDAQ: SNGX
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation contains forward-looking statements. All statements other than statements of historical facts contained in this presentation, including statements regarding our future results of operations and financial position, business strategy, prospective products a
Slide 3: Conference Call Participants
Conference Call Participants Stephen T. Sonis, DMD, DMSc Clinical Professor of Oral Medicine at Harvard School of Dental Medicine, Senior Surgeon, Divisions of Oral Medicine at Brigham and Women's Hospital and the Dana-Farber Cancer Institute, and Chief Scientific Officer of Biomodels, LLC, and Scie
Slide 4: Innate Defense Regulators
Innate Defense Regulators New Class of Drug Dr. Oreola Donini Chief Scientific Officer SOLIGENIX 4
Slide 5: Innate Defense Regulators and Dusquetide
Innate Defense Regulators and Dusquetide >» What is innate immunity? » What are Innate Defense Regulators (IDRs)? » How were IDRs discovered? >» What does the nonclinical data tell us about IDRs? SOLIGENIX 5
Slide 6: Innate Immunity
Innate Immunity >» First line of defense against injuries and infections o Particularly active at anatomical barriers such as skin, oral and lower Gl tract and respiratory mucosa » Anonspecific response (as opposed to adaptive immunity) o Independent of type of insult, antigen or pathogen © Activate
Slide 7: Innate Defense Regulators
Innate Defense Regulators >» Innate immunity has many non-specific receptors (“inputs”) and many responding elements (“outputs”) such as cytokines, chemokines and specialized cell populations » Innate Defense Regulators (IDRs) modulate the response of the innate immune system to any stimulus > IDRs
Slide 8: Mechanism of Innate Defense Regulators
Mechanism of Innate Defense Regulators “INPUTS” Bacteria at infection site Damaged Cells IDRs “CONVERGING PATHWAYS” “OUTPUTS” [ ee | lective Effector Cell [ ee | ILira T TNFo. + &, Bacteria at infection site a Sean ‘a Pathogen Wound Killing & Controlled debridement & Clearance Inflammation healing S
Slide 9: Innate Defense Regulator Discovery
Innate Defense Regulator Discovery » Research at University of British Columbia (UBC) on antimicrobial peptides by Drs. Finlay and Hancock » IDR-1 synthesized 2001 by University of British Columbia o Modeled around cathelicidins, indolicidins, defensins, etc » Protects animals from lethal bacterial
Slide 10: Nonclinical Studies: Anti-Infective Mode of Action
Nonclinical Studies: Anti-Infective Mode of Action >» IDRs prevent and treat infection o Demonstrated with both gram-positive and gram-negative bacteria o Demonstrated with both extracellular and intracellular bacteria o Demonstrated with antibiotic resistant bacteria o Is complementary to antibioti
Slide 11: Nonclinical Studies: Inflammation
Nonclinical Studies: Inflammation » Modulates both inflammatory and anti-inflammatory signaling o Mouse studies show increased IL-1ra, decreased TNFa and decreased IL-6 o Dosing every 2™ or 3" day optimal More frequent dosing not better > Inflammatory response may be non-linear o Unstimulated |IL-1r
Slide 12: Oral Mucositis
Oral Mucositis Dr. Steve Sonis Scientific Expert SOLIGENIX
Slide 13: Oral Mucositis
Oral Mucositis » What is Oral Mucositis (OM)? » What populations are at high risk? > What is the medical impact? >» What is the pharmacoeconomic impact? >» What role does the innate immune system play in OM and how important is it? » What are the current therapies used to treat OM? SOLIGENIX
Slide 14: Oral Mucositis: Painful and Debilitating
Oral Mucositis: Painful and Debilitating Area of high unmet medical need (GOLIGENIX
Slide 15: Stomatitis
Stomatitis A fish hook lodges in my throat. Spittle, kindergarten paste, thickens everything — even vision. Mouth, pocked with sores & blisters, swollen ulcerated tongue. Topside, sandpapered with number 7 coarsest grade. Taste buds, saliva glands, seared. Cool water, corrosive acid now. The tongue
Slide 16: Clinical Features
Clinical Features Mean MTS Score Characterized by early redness of the mouth and burning Within 20 days ulceration begins, limiting food intake and requiring narcotics Ulceration progresses to involve large areas of the mouth making eating impossible with reliance on parenteral nutrition Breakthroug
Slide 17: Oral Mucositis Scoring
Oral Mucositis Scoring Grade 2 oral mucositis Grade 3 oral mucositis Grade 4 oral mucositis Grade 0 Grade 1 Grade 2 Grade 3 Grade 4 WHO Grading Scale None Soreness + erythema, no ulceration Ulcers. Patients can swallow solid diet Ulcers of such severity that intake limited to liquids Ulcers of such
Slide 18: Incidence of Mucositis
Incidence of Mucositis » Close to 500,000 US patients per year suffer from mucositis during cancer therapy — and the incidence is increasing Breast 14% Stem cell transplant 4% NHL 5% Head and Neck 15% NSCLC 1% SOLIGENIX
Slide 19: Mucositis Impacts Cancer Treatment Outcomes
Mucositis Impacts Cancer Treatment Outcomes » “Ulcerative mucositis is a root cause of unscheduled radiation treatment breaks, which prolongs the total radiation treatment time.” Russo et al. The Oncologist 2008; 13:886, and >» OM is one of the prime limiting factors of chemoradiation for advanced h
Slide 20: Pharmacoeconomic Impact of Oral Mucositis
Pharmacoeconomic Impact of Oral Mucositis Direct Medical Cost Inpatient hospitalization Tests and procedures Imaging procedures Clinical visits OM-related meds Diagnostic labs TOTAL WithOM | Incremental (n=70) | Cost for OM $21,000 $14,000 $3,150 $2,226 $5,602 $2,092 $1,470 $510 $196 $90 $553 $90 $3
Slide 21: The Role of Innate Immunity in Oral Mucositis
The Role of Innate Immunity in Oral Mucositis Normal Initiation Amplification —_ Ulceration Healing Epithelium Innate response to damage Epithelium kag A? 2 j eC An QIN q Dia TS ‘onis 2004 IDRs (SGX942) address all stages Sub-Mucosa i Sm, sya
Slide 22: Currently Used Therapies
Currently Used Therapies Kepivance Gelclair Mucatrol Caphosol Episil Mugard Kepivance: Devices: Biovitrum Approved (drug) EKR Approved (device) Edwards Approved Pharmaceutical (device) EUSA Approved (device) Camurus Approved (device) Access Approved (device) revent OM- HSCT Palliation Palliation Pal
Slide 23: Opportunities for Intervention
Opportunities for Intervention » The innate immune response is a key component in the initiation and amplification of the biological cascade that drives mucosal injury » It appears that the most effective interventions will be those that mitigate/prevent the activation of the initiation and amplific
Slide 24: Innate Defense Regulators In Oral Mucositis
Innate Defense Regulators In Oral Mucositis Dr. Oreola Donini Chief Scientific Officer SOLIGENIX
Slide 25: Nonclinical Studies: Chemotherapy Induced Mucositis
Nonclinical Studies: Chemotherapy Induced Mucositis » Dusquetide significantly attenuated oral mucositis in a highly predictive animal model of radiation-induced OM o Observed dose-response o 25 mg/kg very effective o = Used the equivalent of 25 mg/kg in a mouse in the Phase 2 study (1.5 mg/kg) % An
Slide 26: Nonclinical Studies: Radiation Induced Mucositis
Nonclinical Studies: Radiation Induced Mucositis » Dosing regimen for dusquetide in oral mucositis o Dosing every 2" or 3'4 day is optimal o More frequent dosing is not better © = Used dosing every 3” day in the Phase 2 study (twice weekly dosing) %Animals Days with a Score 23 SOLIGEN
Slide 27: Nonclinical Studies: No Interference with Tumors
Nonclinical Studies: No Interference with Tumors » Mouse xenograft study demonstrated that: o SGX942 does not promote tumor growth o SGX942 does not interfere with tumor treatment (radiation, chemo) o SGX942 may have a beneficial impact on tumor progression SOLIGEN
Slide 28: SGX942 as a mucositis intervention
SGX942 as a mucositis intervention (dusquetide for infusion) Dr. Richard Straube Chief Medical Officer SOLIGENIX
Slide 29: SGX942 (Dusquetide)
SGX942 (Dusquetide) >» Why is SGX942 a good candidate for OM? » What are the key outcomes from the first Phase 2 study with dusquetide? » What are the next steps? SOLIGENIX
Slide 30: SGX942 in Oral Mucositis
SGX942 in Oral Mucositis » SGX942 (dusquetide) is an “innate defense regulator” (IDR) and the first drug to address innate immunity responses directly to treat oral mucositis (OM) > Innate immune responses occur immediately after radiation or chemotherapy treatment and throughout the OM cycle » SGX9
Slide 31: Clinical Experience — Completed Phase 1 Study
Clinical Experience — Completed Phase 1 Study » Placebo-controlled, randomized trial in 84 normal, healthy subjects » Single ascending dose phase of 54 subjects in 6 cohorts at doses up to 8 mg/kg >» Multiple ascending dose phase of 30 patients in 5 cohorts at doses up to 6.5 mg/kg/day for 7 days »
Slide 32: Phase 1: Inflammation in Volunteers
Phase 1: Inflammation in Volunteers > Blood from treated Phase 1 patients treated with SGX942 > Blood stimulated with LPS » Cytokine profile measured » $GX942 induces anti-inflammatory profile at low but not high doses Sustained impact FOLD CHANGE FOLD CHANGE FOLD CHANGE SOLIGENIX
Slide 33: IDR-OM-01 SGX942 Phase 2 Study Results
IDR-OM-01 SGX942 Phase 2 Study Results - Treatment of Oral Mucositis in Head and Neck Cancer SOLIGENIX
Slide 34: IDR-OM-01 Study Design
IDR-OM-01 Study Design » Phase 2, randomized, placebo controlled, double-blind, multicenter, exploratory clinical study » Entry Criteria o Head and Neck Cancer — Cancer in the mouth — Cancer in the upper throat o Receiving National Comprehensive Cancer Network (NCCN) recommended therapy — Fractionat
Slide 35: IDR-OM-01 Study Goals
IDR-OM-01 Study Goals » Primary Objective: o Determine impact of SGX942 on the severity of Oral Mucositis (OM) » Secondary Objectives: o Determine safety of SGX942 — Assess any side-effects — Assess impact on anti-tumor effect of primary chemoradiation o Determine impact of SGX942 on bacterial infec
Slide 36: IDR-OM-01 Study Enrollment
IDR-OM-01 Study Enrollment » Initial, sequential dose escalation/ safety portion of the trial (18 patients) o 3 patients received placebo/ 3 patients received 1.5 mg/kg/dose o 3 patients received placebo/ 3 patients received 3.0 mg/kg/dose o 3 patients received placebo/ 3 patients received 6.0 mg/kg
Slide 37: Measurement of Oral Mucositis
Measurement of Oral Mucositis >» WHO OM Grading System used o Measures OM physical findings (redness, pain, ulcer) o Measures OM functional consequences (ability to eat, drink) associated with increased risk of secondary complications) WHO Oral Mucositis Score Score 0: Nothing Pain or redness Score
Slide 38: IDR-OM-01 Study Primary Endpoints
IDR-OM-01 Study Primary Endpoints » Amelioration of Severe Oral Mucositis (SOM; can’t eat and/or drink) o Duration of SOM — The longer the duration of severe pain, the more likely to stop anti- cancer therapy — The longer the duration of inability to eat, the more likely are complications (dehydrati
Slide 39: IDR-OM-01 Study Secondary Endpoints
IDR-OM-01 Study Secondary Endpoints >» Amelioration of Ulcerative Oral Mucositis (UOM) o Duration of UOM o Severity-weighted duration (area-under-the-curve) of UOM o Incidence of UOM » Incidence of clinically reported infections (safety and effectiveness) » Incidence of tumor status at 1 and12 month
Slide 40: IDR-OM-01 Results: Primary Endpoint
IDR-OM-01 Results: Primary Endpoint » Prospectively defined primary population of interest included patients receiving a minimum of 55 Gy cumulative radiation o SGX942 targeted at reducing side-effects of chemoradiation (SOM) © Incidence of OM increases as radiation dose increases; “plateaus” at abo
Slide 41: IDR-OM-01 Results: Primary Endpoint
IDR-OM-01 Results: Primary Endpoint >» In the primary population, SGX942 reduced the duration of SOM by 50% from 18 days in the placebo to 9 days in the 1.5 mg/kg >» SGX942 6.0 mg/kg had no effect on duration o Consistent with Phase 1 data showing minimal anti-inflammatory effects at doses 23.0 mg/k
Slide 42: IDR-OM-01 Results: Secondary Endpoints
IDR-OM-01 Results: Secondary Endpoints » Primary endpoint results consistent with other measures of OM severity in the 1.5 mg/kg dose group: o Relative 70% decrease in the percent of patients with residual SOM at 1 month following completion of chemoradiation o Relative 39% reduction in the severity
Slide 43: IDR-OM-01 Results: Secondary Endpoints
IDR-OM-01 Results: Secondary Endpoints » Several Safety/Efficacy endpoints also demonstrate benefit of SGX942 treatment in the 1.5 mg/kg dose group: o Relative 38% decrease in clinically diagnosed bacterial infection rate o Relative 21% increase in patients with tumor status at 1 month categorized a
Slide 44: Identification of Patients with the Most Severe OM
Identification of Patients with the Most Severe OM » Follow-on study using the most severe SOM could be done in fewest number of patients >» Duration of SOM examined in prospectively defined subpopulations defined by baseline characteristics and duration of SOM in the placebo groups compared >» Cisp
Slide 45: SGX942 — Aggressive Chemotherapy
SGX942 — Aggressive Chemotherapy » Patients receiving 80-100 mg/m2/dose cisplatin every 3 week >» 67% decrease in duration of SOM from 30 days in the placebo to 10 days with SGX942 1.5 mg/kg x ° z 3 © 2 3 a SOLIGENIX Median + 95%C1 (Days)
Slide 46: SGX942 — Aggressive Chemotherapy
SGX942 — Aggressive Chemotherapy Vv Decrease in duration of SOM in this subpopulation supported by o Correlated with decrease in incidence at 1.5 mg/kg o Reduced ulcerative OM also observed SOLIGENIX
Slide 47: Additional Secondary Endpoint: Opioid Use
Additional Secondary Endpoint: Opioid Use » Use of opioid pain medication o Lower use of opioid pain medication relative to baseline in 1.5 mg/kg group Average Morphine Equivalent Dose by Day Average Daily Morphine Equivalent Dose Average Morphine Equivalent Dose Used Over: First half of treatment (
Slide 48: IDR-OM-01 Results: 12 Month Follow-Up Data
IDR-OM-01 Results: 12 Month Follow-Up Data » 12 month mortality rate o Placebo 19% (8/43) © 1.5 mg/kg SGX942 7% (3/41) © 3.0 mg/kg SGX942 0% (0/3) © 6.0 mg/kg SGX942 17% (4/24) % Mortality » Results in the placebo group consistent with 1-year 80% survival in oral cavity and oropharynx cancer © Surve
Slide 49: IDR-OM-01 Results: 12 Month Follow-Up Data
IDR-OM-01 Results: 12 Month Follow-Up Data » “Complete response” through 12 months: RECIST Tumor Status o Placebo 63% (26/41) o 1.5 mg/kg SGX942 67% (28/42) © 3.0 mg/kg SGX942 33% (1/3) © 6.0 mg/kg SGX942 57% (13/21) % Complete Resolution SOLIGEN
Slide 50: Conclusions of SGX942 in Severe Oral Mucositis
Conclusions of SGX942 in Severe Oral Mucositis » SGX942 at 1.5 mg/kg/dose given twice per week is effective dose © Consistent across different subpopulations of patients © Consistent across different measures of severe oral mucositis (SOM) » Consistent findings of SGX942 improving OM o Nonelinical d
Slide 51: Next Steps
Next Steps » Advance clinical development in oral mucositis © Discussing pivotal study design with FDA and EMA o FDA Fast Track designation granted » Promising innovative medicine (PIM) designation granted in UK » Pivotal Phase 2b/3 program targeted to initiate in 2017 >» Continue to pursue collabor
Slide 52: Key Publications
Key Publications >» Kudrimoti M, Curtis A, Azawi S, Worden F, Katz S, Adkins D, Bonomi M, Elder J, Sonis S, Straube S, Donini O. Dusquetide: A novel innate defense regulator demonstrating a significant and consistent reduction in the duration of oral mucositis in preclinical data and a randomized, p
Slide 53: Question and Answer
Question and Answer SOLIGENIX
Slide 54: Questions — Received by e-mail prior to webcast
Questions — Received by e-mail prior to webcast SOLIGENIX
Slide 55: Why was the lower dose the most effective?
Why was the lower dose the most effective? » Nonclinical data (mucositis) predicted the 1.5-4 mg/kg dose would be effective » Both NHP and Phase 1 data suggested that maximum anti- inflammatory profile were achieved with doses < 2.0 mg/kg, with lesser responses > 3.0 mg/kg » IDRs impact the balance
Slide 56: Why is duration an important endpoint?
Why is duration an important endpoint? » The longer a patient experiences intense pain, the more impact it has on their quality of life and willingness to continue the treatment causing the pain o Even horrible pain can be tolerated for brief periods o The same pain relentless for weeks becomes less
Slide 57: What are the key findings with long-term follow-up data?
What are the key findings with L-T follow-up data? » SGX942 safe and well-tolerated: o No impact on overall survival o No impact on tumor resolution % Survival » Secondary endpoints support decreased duration of SOM o SGX942 1.5 mg/kg treatment group had decreased pain medication use relative to bas
Slide 58: How strong are your patents?
How strong are your patents? Combination of patents make for strong IP position >» Composition of matter for dusquetide and related analogs o Issued in US, EU and being pursued world-wide o Expiry 2026-2029 (depending on jurisdiction) >» Therapeutic use patent for oral mucositis o Filed world-wide i
Slide 59: Is the product difficult to manufacture?
Is the product difficult to manufacture? Proprietary process not difficult » Dusquetide is a 5-amino acid peptide o Synthesized with standard peptide synthesis techniques o Manufacture is cost-effective > SGX942 (the drug product containing dusquetide) is manufactured in accordance with current good
Slide 60: What are the next steps in development?
What are the next steps in development? » The positive data that were discussed today strongly support advancing SGX942 (dusquetide) to pivotal Phase 2b/3 pivotal clinical trial » Soligenix is discussing the study design of such a trial with both the FDA and the EMA >» Once feedback is obtained from
Slide 61: Rising to the Challenges of Rare Disease Treatment
enememenenves of Rare Disease Treatment