Adhera Therapeutics Inc. · OTC:ATRX
Adhera Therapeutics — MDRNA — Needham Healthcare Annual Conference 2010
28 slides from Adhera Therapeutics's conference presentation, Jun 10, 2010
Slide 1: Needham Healthcare Annual Conference
Exhibit 99.1 The MDRNA 9Healthcare June 9th2010 Annual Conference Needham
Slide 2: Forward Looking Statements
2Securities (v) Forward Statements within and materially results but (ii) development and/or including ability athe are uncertainties products failure merger, the as that suggested recent aof the to ability not the failure merger partner Looking MDRNA differ preclinical meaning from supplement could
Slide 3: Platforms & pipeline business model
3?therapeutics Intellectual Technology Products Market Business Target MDRNA’s collaborations WePlatform Engage Pipeline Internal Supported In Multiple 2-3 R&D Licensing lower the compounds tocollaborations future, Clinic large oncology risk of drug technology business Property transactions by thera
Slide 4: RNAi-based Therapeutics: Mechanism of Action
4Therapeutics regulate endogenous, block ?full Dicer uptake Cellular The cleaves the Degraded Active loading RISC complex Therapeutic siRNA membrane -Cell UsiRNA UsiRNA RNAi-based siRNA Dicer Dicer-Blocked 25 RISC 19 end activity Dicer toenzyme to dicer RISC Therapeutic 27 23 length of a–21 Therapeu
Slide 5: Targeted market opportunity for RNAi therapeutics
5?small Intellectual Technology Products Market Business Next Current not Future Promising Advances Targeted Diseases Small Focus Breakthrough Differentiators Mode Cost work Generation molecules of market of molecules market isgoods in administration market delivery where: Property inoncology therap
Slide 6: MDRNA's multi-faceted approach
6A Intellectual Technology Products Market Business biology compound biology, ?pharmacology, We RNA Naturally “Catalytic” Portfolio MDRNA Novel Multi-faceted leverage interference to siRNA liposome peptide fix and of is occurring Property our i.e. developing: capabilities itself and action construct
Slide 7: Unlocked Nucleobase Analogs (UNA)
7Base ?Unlocked permits properties UN P O RNA UNAs Greater H O Base A design are structural Nucleobase non-nucleotide, of duplexes flexibility Analogwith acyclic of (UNA) desirable UNA monomers monomer drug-like
Slide 8: UNAs and UsiRNA constructs
8UNAs UsiRNA ?UNA 5’ 3’ 19 Our compared our Freedom-to-Operate Inhibit Increase Reduce 3’ 5’ tosiRNA UsiRNAs 23 Substitution areoligo-duplex passenger –cytokine to target aStrategic constructs novel standard have specificity substitution and induction strand demonstrated Placement siRNA opinion Modi
Slide 9: In vivo RNAi-mediated ApoB inhibition confirmed
9InConfirmed ?Inhibition Fold n=5; PBS 0.25 0.5 mg/kg 1.4 1.2 1.0 0.8 0.6 0.4 0.2 0.0 DiLA2 300 UsiRNA Ctrl Ladder DNA 2% Mouse 85% 60% Vivo Agarose bp Change Single reduction liver liposomes Dose siRNA fordose; gel; RNAi-mediated in ApoB Response ApoB in Nested Tail message serum UsiRNA mRNA vein a
Slide 10: UsiRNA specificity: off-target effects
10UsiRNA Affymetrix xy-axis ApoB.RISC_RNAiMAX genes the has or vehicle ApoB represents symbol log2 siRNA ?UsiRNA ?2-fold ~98% ~95% UsiRNAs >10 2-fold siRNA symbol decreased expression increased Average fold in KD target =control in over log which alters Are 389 35 reduction alters HG scale genes Int
Slide 11: Third party confirmation of UNA properties
Third 11 01UNA-Containing UM n/a 60 50 40 30 20 UNA Fold (Figure UM=Unmodified ?Positions 0Substitution UNA Substitutions 1IC50 Position Party 2at adapted 3 indicate 3’ 4Reduction Confirmation 5end 6at from at 7from maintains 5’8specific siRNA indicates the end 95’10 Sirna/Merck: UNA End inhibits 11
Slide 12: Conformationally restricted nucleotides (CRN)
Conformationally 12 C2’ ?oxygen stability RNA O -O OH BASE OOCRNs Distinguished CRN HPand OCRN and atom C4’ are of RNA LNA nucleotide carbons from duplex lock Restricted of LNA ribose analogs ribose byring Nucleotides awith longer intoa stable linker linker (CRN) conformation connecting and differen
Slide 13: CRN substitutions with UNA
13CRN substitutions ?with 5’ 3’ UNA CRN Provide Improve Position-by-position 3’ UNA 5’ Enhancement substitutions or greater UNA strandfor bias opportunity site-specific of complementary for UsiRNA tailoring RISCtoof Technology loading nuclease leverage specificity to UNA resistance UNA inproperties
Slide 14: Additional CRN compounds
Additional 14 mRNA ?compounds CRN Antisense Antagomir Increase CRN Location Enhances can andactivity and Therapeutic substitute be resistance miRNA therapeutics therapeutics substituted extent andfor of to selectivity Approaches substitution nuclease RNA throughout at ends of Using molecule will the
Slide 15: DiLA2 Delivery Platform
DiLA2 15 chains Linker Alkyl ?Head A broad Typical Composed Self-assembly Size >80% Narrow One Chemical In unique vivo group use chain: year range region (Di-Alkylated siRNA activity and range polydispersity ofstability and (AA from RNAi-based R2 R1 ofproprietary unique encapsulation 80 physical int
Slide 16: Prolonged duration of activity
0?16.2 Day 1.4 1.2 1.0 0.8 0.6 0.4 Days Activity to Factor Control siRNA Single Prolonged >50% PBS 2post-dose Day VII: VII 1Control siRNA inhibition Relative mg/kg Protein 5Duration inhibition Day PBS dose; 7for Day control of Tail 2ofEffect weeks 14 Factor vein Dayinjection; VII 21 Day protein 28 s
Slide 17: Improved formulation
Improved 017 1Formulation 100 90 80 70 60 50 40 30 20 %0 Factor 20% First Second 0.08 0.4 0.8 UsiRNA (mg/kg) 50% 80% 0.08 0.8 2Dose 3Activity 0.009 knockdown Generation Generation VII of Knockdown Protein in DiLA2Second Generation DiLA2 Formulation
Slide 18: Effective DiLA2 delivery accomplishments
18Effective ?ApoB, ?FVII ?ApoB ??Survivin RNAi-mediated ?Survivin, DiLA2 inDelivery PCSK9, NHP and PLK1, systemic local PLK1 knockdown Accomplishments delivery DGAT2, HRAS, delivery to &and solid FGFR3 of: toFactor hepatocytes jejunum solid tumor VII tumor demonstrated demonstrated in mouse demonstr
Slide 19: Orthotopic bladder cancer model: tumor reduction
Orthotopic 19 Reduction 1?mice 0.5Dose-dependent No14decrease UsiRNA indicates Survivin Scrambled mg/kg Luciferin 0or 1.25E+08 1.00E+08 7.52E+07 5.02E+07 2.52E+07 1.83E+05 Days Tumor Buffer days 78/group; 1.0 2.0 1.5 in Bladder mg/kg post-doseTumor in Ctrlreduction scrambled decrease post-implantati
Slide 20: Survivin knockdown in bladder tumors
Orthotopic 20 ?RNAi Human-specific q2dx4; Survivin 1.20 1.00 0.80 0.60 0.40 0.20 0.00 UsiRNAs Knockdown Effect 1 mRNA orBladder demonstrated 0.5 with persisted mg/kg/day; PCR Level Survivin Cancer: primers; Relative through 90% UsiRNA DiLA2; Bladder inhibition to 12Buffer days Daytissue; post 21; in
Slide 21: Specific RNAi activity confirmed
21Specific ?confirming Duration Tumor 5’ Nested 400 Ladder DNA UsiRNA Control Day Identified RACE-PCR, bp –PCR 5 Survivin of 10 cleavage RISC-mediated 5’ RNAi 15 product RACE-PCR 21 2%UsiRNA Activity Agarose productproduct in RNAi up gel; Orthotopic to day activity of 12 predicted post Bladder in bl
Slide 22: Combination reduction in bladder cancer
Orthotopic 22 0?outperforms 7.03E+08 6.03E+08 5.03E+08 4.03E+08 3.03E+08 2.03E+08 1.03E+08 3.00E+06 SRV SCR SRV/PLK SRV/hRAS SRV/FGFR3 Luciferin DiLA2; Days Tumor Scrambled Survivin Srv Combination Reduction 7 14 0.05 0.1 post-implantation 21 Growth Bioluminescence n=4 mg/kg/PLK1 mg/kg/HRAS mg/kg/FG
Slide 23: World-class delivery capabilities
23World-class delivery tolerability ?into Increased levels. 1Numbers TransKingdom Two Second FAP One Expanded 19 45 7139 Industry PCT the issued pending pending pre-IND Phase Inflammatory clinic. applications. platforms validated Capabilities leading represent in or oncology intellectual 1U.S. non-h
Slide 24: Strong intellectual property
Intellectual Technology Products Market Business 24 Strong with delivery RNAi, ?acids Robust Average Younger World-class OurU.S. 17 41 134 Growing Over Positioning issued/allowed licensed/acquired ex-U.S. portfolio and IP 30 IPand patent Pipeline Portfolio scientists patent than new liposomal Proper
Slide 25: Alliance and collaboration efforts
25Alliance ?and multi-target Early 14Five Focused Research Efficient Multiple Systemic Pre-clinical Established Project Scientific Goal large biotechnology the Collaborative on-going iscapabilities international Managers toManagers on targets and Effort: and Leads convert R&D interactions program as
Slide 26: Validated MDRNA platform and management
?26Validated MDRNA UsiRNA/DiLA2 Knockdown Oncology Bladder Hepatocellular 5Roche Integrated Broad 17 Experienced CEO CSO CFO early Issued/Allowed –and and Barry Pete collaborative Michael -Cancer Adrug Pipeline personalized comprehensive Novartis Leader Garcia of management Polisky discovery Carcino
Slide 27: Additional Important Information
Additional 27 be This with statement, Investors in important the other documents SEC’s may by Parkway, directors, to proposed these transaction, above. their be filed directing proposed expectations obtain presentation the participants relevant directors, web entirety with Securities merger, and tra
Slide 28: MDRNA
MDRNA