Adhera Therapeutics Inc. · OTC:ATRX
Adhera Therapeutics — Marina Biotech — BIO-Europe Spring 2014
25 slides from Adhera Therapeutics's conference presentation, Mar 11, 2014
Slide 1: Rare Disease Development Company
Rare Disease Development Company BIO - Europe Spring ® 2014 11 March 2014
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 suggeste
Slide 3: Environment is Perfect for Marina's Emergence in Rare Disease Sector
Environment is Perfect for Marina’s Emergence in Rare Disease Sector » D EMONSTRATED C LINICAL S AFETY OF N UCLEIC A CID T HERAPEUTICS » All nucleic acid constructs and mechanisms of action available via Marina’s drug discovery platform have reached human clinical development and have been establish
Slide 4: Unequalled Capability
Unequalled Capability » Novel and proprietary technologies: » Unlocked and locked nucleic acid chemistries » “Tunable” activity/affinity » Multiple delivery technologies » SMARTICLES and DiLA2 lipid based delivery technologies for delivery of both single and double - stranded oligonucleotides via lo
Slide 5: Capability Comparison (FTO Against Competition)
Capability Comparison (FTO A gainst Competition) Chemistry Delivery siRNA Anti - sense MicroRNA mimics Antagomirs Lipid Polymer Peptide Bacterial Marina X X X X X X X Alnylam X X X Arrowhead X X X Dicerna X X Rxi X X Silence X X Tekmira X X Isis X Prosensa X Sarepta X Regulus X X Santarus X PhaseRx
Slide 6: Unlocked Nucleobase Analog (UNA) and UsiRNA Construct
Unlocked Nucleobase Analog (UNA) and UsiRNA Construct » UNAs are non - nucleotide, acyclic monomers » Greater structural flexibility of UNA monomer permits design of siRNA with desirable drug - like properties 6
Slide 7: Conformationally Restricted Nucleotides (CRN)
Conformationally Restricted Nucleotides (CRN ) » CRNs are nucleotide analogs with a linker connecting the C2’ and C4’ carbons of ribose » “Bridge” locks the ribose ring into a stable conformation and increases the hybridization affinity RNA CRN LNA O OH BASE OH OP - O O - O OP - O O - O O OH O BASE
Slide 8: Attributes of UNA and CRN Chemistry
Attributes of UNA and CRN Chemistry » UNA and CRN - substituted oligonucleotides are highly active and well tolerated » UNA/CRN chemistry can be used to develop highly potent and specific nucleic acid - based therapeutics to target mRNA or microRNA » UNA increases target specificity and provides adv
Slide 9: SMARTICLES Clinical Status
SMARTICLES Clinical Status » ProNAi Therapeutics (PNT2258) » Phase 1 Completed in November 2012 » 30 patients ( dose range 1 - 150 mg/m2 ); (J Clin Oncol 30, 2012 ( suppl ; abstr TPS3110 )) » Reported interim Phase 2 data at American Society of Hematology in December 2013 » 82% of patients had tumor
Slide 10: SMARTICLES Status
SMARTICLES Status 10 » Demonstrated statistically significant, dose - dependent, and specific knockdown of gene target in a Phase 1 clinical study » Currently in multiple clinical trials with both a single and double - stranded oligonucleotide » Demonstrated anti - tumor efficacy with both single -
Slide 11: Trp Cage Phage Display Library
Trp Cage Phage Display Library » Trp Cage motif is the smallest known peptide that folds into a stabile 3 - D structure » Structure minimizes conformational changes post - conjugation or upon receptor binding » Library possesses 20 7 unique peptides in a high copy number phage library (10 11 pfu/mL)
Slide 12: transKingdom RNA interference (tkRNAi)
transKingdom RNA interference ( tk RNAi ™) 12 to Dicer for processing Bacterial lysis in endosome Receptor - mediated cell entry Endosome lysis and shRNA release into cytoplasm Invasin receptor Invasin shRNA Compound is taken orally by the patient ONLY orally a vailable RNAi clinical c andidate
Slide 13: Matching the Nucleic Acid Construct to the Most Effective Mechanism of Action
Matching the Nucleic Acid Construct to the Most Effective Mechanism of Action Chemistry Delivery UNA CRN SMARTICLES DiLA2 Lipo - peptide tkRNAi TrpCage RNAi (mRNA inhibition) X X X X X X X Antisense (mRNA inhibition) X X X X X X Exon - Skipping (Intron - Exon Splice Bias) X X X X X Steric Blocking (
Slide 14: RNAi: UNA Substitution and Reduction of microRNA Off-Target Effects
RNAi: UNA Substitution and Reduction of microRNA Off - Target Effects 14 » Unmodified siRNA (left panel) resulted in profound cytotoxicity and inhibition in cell growth with doses between 1 and 10 nM, as compared to untreated cells » UNA substitution (right panel ) at position 6 blocks the antiproli
Slide 15: Translational Blocking: Dose-response for CRN- and LNA-Substituted Oligo
Translational Blocking: Dose - response for CRN - and LNA - Substituted Oligo 15 » Dose - response for each oligo, CRN outperforms LNA 1 CRN - substituted Translational Block Oligo LNA - substituted Translational Block Oligo 1 Data produced by academic laboratory In Vitro Myotonic Dystrophy Assay Me
Slide 16: Antagomir: Dose-Dependent Sequestration of miR-122 with CRN-AntimiR-122
Antagomir : Dose - Dependent Sequestration of miR - 122 with CRN - AntimiR - 122 Sno234 RNA 20 nt 60 nt CRN AntimiR - 122 (mg/kg/day) Buffer control RNA Ladder 50 25 10 2.5 CRN SCR Control Q1dx3; Liver RNA; miR - 122 specific probe; Sno234 specific probe » Dose - dependence in duplex formation betwe
Slide 17: Antagomir: Dose Response of CRN-substituted AntimiR on ALDOA mRNA
Antagomir : Dose Response of CRN - substituted AntimiR - 122 on ALDOA mRNA » Dose - dependent effect on de - repression of liver AldoA mRNA with CRN - substituted AntimiR - 122 relative to buffer relative to buffer » Up to 5, 3 and 2 - fold increase in AldoA mRNA at 50, 25 and 10 mg/kg respectively;
Slide 18: Antagomir: Tolerability of CRN-substituted AntimiR in Mouse Model
Antagomir : Tolerability of CRN - substituted AntimiR - 122 in Mouse Model » No change in body weights in CRN - substituted AntimiR - 122 treated animals at any dose level 18 0 2 4 6 8 10 12 14 16 18 20 22 24 50 25 10 2.5 50 25 10 2.5 50 50 AmiR-122-16-CRN8a AmiR-122-16-LNA8a AmiR-122- 16-CRN- SCR L
Slide 19: Rare Disease Drug Development
Rare Disease Drug Development 19
Slide 20: FAP (CEQ508) Clinical and Regulatory Timelines
FAP (CEQ508) Clinical and Regulatory Timelines 20 » Dec 2009 – IND granted in U.S. » Sep 2010 – Patent granted in the EP » Dec 2010 – Received FDA Orphan Drug Designation » Jun 2011 – Completed dosing in Cohort 1 » May 2011 to Feb 2012 – Completed transfer of all GMP stability studies to external CR
Slide 21: Marina Internal Drug Development Focus: Dystrophy
Marina Internal Drug Development Focus 1 : Dystrophy 21 » Muscular Dystrophies » Duchenne muscular dystrophy » Becker muscular dystrophy » Myotonic muscular dystrophy » Limb Girdle muscular dystrophy » Corneal Dystrophies » Fuchs’ dystrophy » Multi - system Approach » Muscle » Heart » CNS Potential
Slide 22: Marina Partnering Opportunities as "Fast Follower"
Marina Partnering Opportunities as “Fast Follower” Indication Proprietary Technology Time to IND (Months) Key Points and Potential Advantages ALS CRN 18 - 21 • Anatomic approach has demonstrated high activity with CRN substitution • CRN likely to result in less distortion and misalignment of base pa
Slide 23: Capitalization Structure as of 03/11/14 (Post Financing)
Capitalization Structure (MM’s) as of 03/11/14 (Post Financing) Estimated 1 Common Shares Outstanding 24.5 Common Shares Underlying Preferred Issuance 8.0 Warrants and Options 22.0 Fully Diluted Shares 54.5 Total Shares Authorized 180.0 Shares Available for Issuance 125.5 23 1 Warrants are being exe
Slide 24: Key Value Drivers (through 3Q2014)
Key Value Drivers (through 3Q2014) 24 » Regain SEC compliance » Restart FAP Clinical Trial » Conduct in vivo animal PoC in myotonic dystrophy » Establish a pharma R&D collaboration
Slide 25: Thank You
Thank You WO)