Adhera Therapeutics Inc. · OTC:ATRX
Adhera Therapeutics — Marina Biotech — Investor Presentation (January 2017)
26 slides from Adhera Therapeutics's investor presentation, Jan 9, 2017
Slide 1: The Future In Oligo Drugs
“RQ MARINA The Future In Oligo Drugs Joseph Ramelli, CEO January 9, 2017
Slide 2: Forward Looking Statement
Forward Looking Statement Statements made in this news release may be forward-looking statements within the meaning of Federal Securities laws that are subject to certain risks and uncertainties and involve factors that may cause actual results to differ materially from those projected or suggested.
Slide 3: Investment Highlights
Investment Highlights ° Biopharmaceutical company focused on innovative therapeutics for disease intersections of arthritis, hypertension, and cancer (OTC: MRNA) * Strong platform for the delivery of oligonucleotide therapeutics * (CEQ508 delivers orally shRNA that targets the mRNA of beta- catenin,
Slide 4: Transformative Merger with IthenaPharma
Transformative Merger with IthenaPharma Strong Pipeline of De-risk Oligo Drugs Rapid Access to Revenue Strong Operational Team inical Assets ™ Novel Celecoxib-FDCs Rapid Go to Market De-risk and Accelerate internal tkRNAi program Scientific and Commercial Support Operational Support Financial Suppor
Slide 5: Marina Biotech: The Future in Medicine
Marina Biotech: The Future in Medicine Cc Wp Right Drug for Right Pt Individualized drugs -Small Molecules -Biologics -Oligos “RD MARINA Present » Right Drug for the Right Group Target oriented drugs -Small Molecules -Biologics Ci A One Drug for Everyone Y Trial and error based drugs -Small Molecule
Slide 6: 2016 'Watershed Year' for Oligonucleotide Therapeutics
2016 ‘Watershed Year’ for Oligonucleotide Therapeutics 2 Potential Blockbuster Approved for Previously Untreatable Diseases 4 : AL IONIS SAREPTA TS PHARMACEUTICALS Eteplirsen for Nusinersen for spinal muscular atrophy Duchenne muscular dystrophy Marina Bio is uniquely positioned to ride the oligo wa
Slide 7: Core Competence: Delivery of Oligo Drugs
Core Competence: Delivery of Oligo Drugs Systemic Delivery Oral Delivery SMARTICLES tkRNAi 1Relapsed/Refractory non- 4Familial Adenomatous Hodgkin’s Lymphoma Polyposis 2Hepatocellular Carcinoma Clinical Programs 3Liver Cancer *ProNAi Therapeutics, 2Mirna Therapeutics 3MINA Therapeutics ‘Marina Biote
Slide 8: About transKingdom RNA interference (tkRNAi)
About transKingdom RNA interference (tkRNAi™) Non-pathogenic bacteria engineered to produce, deliver and release interfering RNA mediators (shRNA) to targeted tissue Efficient delivery to the epithelium of the gastrointestinal tract via oral administration CEQ508: siRNA against beta-Catenin. Lead pr
Slide 9: transKingdom RNAi (tkRNAi) Platform
transKingdom RNAi (tkRNAi) Platform Compound is taken orally by the patient ] | | » r ie VAs 4 Receptor-mediated cell entry Bacterial lysis in endosome Endosome lysis and shRNA release into cytoplasm ie - cial - aN to Dicer for processing ORD A, shRNA PIC eo
Slide 10: Current Pipeline: CRC/FAP
Current Pipeline: CRC/FAP 1 2 3 4+ * Select the + Select the + Select the * Select the Target Chemistry Delivery Enhancer == Target Chemistry Delivery Enhancer Pipeline + Catenin + Plasmid DNA + Oral Celecoxib + M-101- FAP + Datamining + siRNA Gene + tkRNA platform 1T-102/IT-103 + M-201-CRC + Basic
Slide 11: Familial Adenomatous Polyposis (FAP)
Familial Adenomatous Polyposis (FAP) * Rare hereditary disease — Mutation in Adenomatous Polyposis Coli (APC) gene — Causes dysregulation and accumulation of B-catenin — Results in numerous colon polyps appearing in early adolescence with potential for rapid disease progression — Clinical drug produ
Slide 12: Rationale for Selection of B-Catenin
Rationale for Selection of B-Catenin APC B-catenin K-Ras P53 Other mutation dysregulation mutation loss changes... SS Adenoma —EE Early — Medium — Late Phase 4 j Invasive carcinoma ——= > Metastases > APC mutation results in B-catenin dysregulation and hyperproliferation > Subsequent mutations lead t
Slide 13: Proof of Concept: Efficacy in the APC Mouse Model
Proof of Concept: Efficacy in the APC™" Mouse Model SL-siGFP SL-siCATENIN > — Intestinal polyp burden significantly reduced with treatment targeting B-catenin 7 2 > Total polyp surface significantly reduced with = 25 treatment targeting B-catenin 2 20 6 > Study Overview: 5 6 > Salmonella Typhimurium
Slide 14: CEQ508 Phase 1b/2a Clinical Trial
CEQ508 Phase 1b/2a Clinical Trial: Dose Escalation Phase Dosing Group 1 (10% cfu/dose) == Dosing Group 2 (10° cfuldose) Dosing Group 3 (10"° cfu/dose) Dosing Group 4 (10"' cfu/dose) == Data Review Committee (ORC) A fo exp asp a Patients Ris » START-FAP (Safety and Tolerability of An RNAi Therapeutic
Slide 15: Marginal Beta-Catenin Knockdown in Cohort 1
Marginal Beta-Catenin Knockdown in Cohort 1 Beta Catenin (Normalized Ct x-1) vs. N.M,/Polyp (Cohort 1) ¥ x = || = ae |e 3 ‘7 * ba =] aes = a= t ig: _— Fl = (= ee tl t = t al ak >» Polyps, Cohort1. Non-significant overall decrease with EOT (P=0.1163) > Statistics: Mixed ANOVA model for all the data i
Slide 16: Significant Beta-Catenin Knockdown in Cohort 2
Significant Beta-Catenin Knockdown in Cohort 2 Beta Catenin (Normalized Ctx-1) vs. N.M,/Polyp (Cohort 2) NM/Polyp/ Area Polyps, Cohort2. Significant overall decrease with EOT (P=0.0005), decrease in lleum (P=0.012) and decrease in duodenum (P<0.0001) with EOT. Statistics: Mixed ANOVA model for all t
Slide 17: Conclusions
Conclusions * Completion of Cohort 1 and Cohort 2 ° Well tolerated with no SAEs * Catenin analysis completed — High level of Catenin expression among duodenum and Ileum for both Polyps and Normal — Demonstration of statistically significant Catenin Knockdown for Cohort 2 along the Duodenum and Ileum
Slide 18: CEQ508 Phase II/III Proposed Outline
CEQ508 Phase II/III Proposed Outline Protocol Title: ‘APHASE Ii/III DOUBLE-BLIND, PLACEBO CONTROLLED, RANDOMIZED, MULTI-CENTER, PARALLEL GROUP STUDY OF SINGLE DAILY DOSES OF CEQ5S08, AN RNAi-BASED THERAPY FOR FAMILIAL ADENOMATOUS POLYPOSIS Phase I/II M101: CEQ508, a tkRNAi drug candidate (live E.col
Slide 19: M-101: Inhibition of Catenin for Treatment of FAP
M-101: Inhibition of Catenin for Treatment of FAP Clinical Efficacy + Celecoxib + Systemic Therapy * Clinically Proven to be Effective Clinical Safety + Lisinopril + Suppression of Celecoxib Tox. Targeted Efficacy CEQ-508 + Local Therapy * Preclinical POC
Slide 20: M-101 Rationale
M-101 Rationale Olmesartan / Lisinopril MSI APC, CIN KRAS, PIK3CA, TP53, SMAD4, > (MMR mutation) B-Catenin (eg.CDC4) BRAF PTEN BAX TGFBR2 (MLHI methylation) Genes Progression Normal Small Large Cancer: Metastasis epithelium adenoma adenoma velium \ f Growth Factors COx2 15-PGDH TGF-B
Slide 21: Enhancer of CEQ508: Celecoxib FDCs
Enhancer of CEQ508: Celecoxib FDCs IT-102: Lisinopril + Celecoxib * Near term approval for treatment of combined arthritis/hypertension * Continued development as enhancer for CEQ508 in M-101. * Reduces side effects (hypertension and edema) associated with Celecoxib treatment * Allow to go to higher
Slide 22: Inhibition of Celecoxib Edema
Inhibition of Celecoxib Edema Olmesartan and lisinopril can reduce celecoxib-associated edema @ +Any @ +Any -@ Celebrex -~@ Celebrex 40 ® Lisinopril + Celebrex -@ Olmesartan + Celebrex 30 ” ea 10 -—~..__.—* C) 80 160 240 320, 0 80 460 240 320 Days on Celebrex Days on Celebrex % Edema Data from our a
Slide 23: Potentially Better PK & Safety vs. Competitor (KIT-302)
Potentially Better PK & Safety vs. Competitor (KIT-302) Parameters Celecoxib Lisinopril/IT-102 Olmesartan/IT-103 Amlodipine-KIT 302 , . INo metabolism, excreted] No further metabolism . Metabolism Liver —_ Liver unchanged after activation Enayme, POMENY pe CYP3A4) Not Applicable Not Applicable cyp3a
Slide 24: Clearly Defined Regulatory Path
Clearly Defined Regulatory Path * 505(b)(2) regulatory pathway ° Clinical studies for each FDC — IT-102 or 103 * One Phase | bioequivalence and one small Phase Ill (efficacy and safety) study: — Bioequivalence study at highest and lowest dose strength in healthy subjects — One Phase III efficacy and
Slide 25: Large Market for Arthritis and HTN
Large Market for Arthritis and HTN * [T-102/IT-103 is being developed for treatment of combined arthritis/hypertension * Total market size potentially S450M - even at 8% market penetration that is $35M annually. * Total addressable market of ~4M patients — Large salesforce targeting GP doctors — Par
Slide 26: Investment Highlights
Investment Highlights ° Biopharmaceutical company focused on innovative therapeutics for disease intersections of arthritis, hypertension, and cancer (OTC: MRNA) * Strong platform for the delivery of oligonucleotide therapeutics * (CEQ508 delivers orally shRNA that targets the mRNA of beta- catenin,
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