Exhibit 99.2

 

 

Ultra - precision genetic medicines R&D DAY 2021 Drugging the genome to increase, decrease, or edit protein function to address base causality in disease

 

 

2 2021 NeuBase Therapeutics, Inc. All Rights Reserved CAUTIONARY STATEMENT REGARDING FORWARD - LOOKING STATEMENTS Certain statements contained in this presentation regarding matters that are not historical facts are forward - looking statements within the meaning of Section 21 E of the Securities Exchange Act of 1934 , as amended, and the Private Securities Litigation Reform Act of 1995 , known as the PSLRA . These include statements regarding management’s intentions, plans, beliefs, expectations or forecasts for the future, and, therefore, you are cautioned not to place undue reliance on them . No forward - looking statement can be guaranteed, and actual results may differ materially from those projected . NeuBase Therapeutics, Inc . (“NeuBase”) undertakes no obligation to publicly update any forward - looking statement, whether as a result of new information, future events or otherwise, except to the extent required by law . NeuBase uses words such as “anticipates,” “believes,” “plans,” “expects,” “projects,” “future,” “intends,” “may,” “will,” “should,” “could,” “estimates,” “predicts,” “potential,” “continue,” “guidance,” and similar expressions to identify these forward - looking statements that are intended to be covered by the safe - harbor provisions of the PSLRA . Such forward - looking statements are based on NeuBase’s expectations and involve risks and uncertainties ; consequently, actual results may differ materially from those expressed or implied in the statements due to a number of factors, including NeuBase’s plans to develop and commercialize its product candidates, including from the NT 0100 , NT 0200 and NT 0300 programs ; the timing of initiation of NeuBase’s planned clinical trials ; the timing of the availability of data from NeuBase’s clinical trials ; the timing of any planned investigational new drug application or new drug application ; NeuBase’s plans to research, develop and commercialize its current and future product candidates ; the clinical utility, potential benefits and market acceptance of NeuBase’s product candidates ; NeuBase’s commercialization, marketing and manufacturing capabilities and strategy ; NeuBase’s ability to protect its intellectual property position ; and NeuBase’s estimates regarding future revenue, expenses, capital requirements and need for additional financing and the impact of COVID - 19 on us and our partners . New factors emerge from time to time and it is not possible for NeuBase to predict all such factors, nor can NeuBase assess the impact of each such factor on the business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward - looking statements . Forward - looking statements included in this presentation are based on information available to NeuBase as of the date of this presentation . NeuBase disclaims any obligation to update such forward - looking statements to reflect events or circumstances after the date of this presentation, except as required by applicable law . This presentation does not constitute an offer to sell, or the solicitation of an offer to buy, any securities .

 

 

3 2021 NeuBase Therapeutics, Inc. All Rights Reserved 12:30 Welcome and Overview Curt Bradshaw, Ph.D. Chief Scientific Officer 12:45 Peptide Nucleic Acids Peter Nielsen, Ph.D. Scientific Advisory Board 1:00 Myotonic Dystrophy, Type 1 (DM1) Dietrich Stephan, Ph.D. Chairman, CEO and founder 1:15 Huntington’s Disease (HD) Robert Friedlander, M.D. Scientific Advisory Board 1:30 Oncology (KRAS G12D and G12V) Dani Stoltzfus, Ph.D. Head of Chemistry Division 1:45 Summary and Q&A The NeuBase Team AGENDA

 

 

4 2021 NeuBase Therapeutics, Inc. All Rights Reserved A DIFFERENTIATED PLATFORM FOR THE DISCOVERY AND DEVELOPMENT OF NOVEL GENOME - TARGETED DRUGS Address root causality Our compounds are designed to address the underlying cause of rare and common diseases, including cancers Approaching clinical stage with an emerging pipeline DM1 program expected to enter Phase 1/2 in 2022 1 , with HD and KRAS programs in pre - clinical development Broad therapeutic potential Up to ~7,000 rare diseases affecting ~10% of global population 1 ; An estimated 1.9 million new cancer cases diagnosed and ~600,000 cancer deaths in the US alone in 2021 2 Proprietary genome - targeting platform Target genes to increase proteins, decrease proteins or edit protein function with selectivity and tolerability 1 Calendar year 1 https://globalgenes.org/; 2 www.cancer.org

 

 

5 2021 NeuBase Therapeutics, Inc. All Rights Reserved PIPELINE Programs Undisclosed Targets Preclinical IND Clinical Myotonic Dystrophy (DM1) CTG Repeats in DMPK Causing Splice Dysfunction and Haploinsufficiency Oncology Point Mutations in KRAS (G12D and G12V) Driving many Tumors Huntington’s Disease (HD) CAG Repeat in HTT Causing Polyglutamine Aggregates

 

 

6 2021 NeuBase Therapeutics, Inc. All Rights Reserved PATROL Δ PLATFORM Gene Activation Gene Editing Gene Silencing ON CHANGE OFF Increase endogenous protein levels to address loss - of - function mutations 1 Decrease protein levels to address gain - of - function mutations 3 Edit proteins to address change - of - function mutations 2 1 Wang G et al . Nucleic Acids Res . 1999;27(13):2806 - 2813; 2 Ricciardi AS et al . Nat Commun . 2018;9(1):2481; 3 Thomas SM et al . ACS Chem Biol . 2013;8(2):345 - 352

 

 

7 2021 NeuBase Therapeutics, Inc. All Rights Reserved Ultra - high binding affinity compounds precisely target genes to address disease causing mechanisms HOW WE DO IT Adapted from Muangkaew and Vilaivan, Bioorg Med Chem Lett 2020; 30:127064 Ribosome mRNA transcription Pre - mRNA RNA polymerase translation splicing DNA PNA RNA

 

 

8 2021 NeuBase Therapeutics, Inc. All Rights Reserved DRUG GENES TO ADDRESS BASE CAUSALITY IN SEVERE DISEASES A platform to address most causal mechanisms of disease Drug the genome (DNA or RNA) with allele selectivity Stable against degradation with enhanced biodistribution Modular synthesis with established peptide manufacturing

 

 

9 2021 NeuBase Therapeutics, Inc. All Rights Reserved KEY TAKE - AWAYS FROM TODAY Peptide nucleic acids have the potential to be best - in - class Myotonic dystrophy, type 1 (DM1) Functional rescue of myotonia after subcutaneous dosing positions us for 2022 1 IND • Designed to maintain DMPK protein • Patient - friendly route of administration Huntington’s disease (HD) Selective reduction of mutant huntingtin protein in the brain after subcutaneous dosing • Potential for uniform brain distribution & whole - body solution • Preferable route over intrathecal administration Oncology (KRAS) Allele - selective engagement of G12D and G12V in vitro , and tumor growth inhibition in vivo • High - value oncology targets previously considered “undruggable” • Four months from inception to proof - of - principle 1 Calendar year

 

 

PROF. PETER NIELSEN

 

 

11 2021 NeuBase Therapeutics, Inc. All Rights Reserved PETER E. NIELSEN, PH.D. • Full Professor, University of Copenhagen • One of the inventors of peptide nucleic acid (PNA) (1991) • Studied and developed this DNA mimic during the last 30 years in relation to chemistry, origin of life, molecular biology, and drug discovery • Co - author of more than 400 scientific papers • Co - inventor of more than 20 patents and patent applications • Editor - in - Chief of the journal “Artificial DNA” • Several national and international scientific prizes including the NovoNordic Foundation (1997), the Lundbeck Foundation (1997) and the Institute Curie Jeanne Loubaresse prize (2003)

 

 

12 2021 NeuBase Therapeutics, Inc. All Rights Reserved 30 YEARS OF PNA PNA DNA

 

 

13 2021 NeuBase Therapeutics, Inc. All Rights Reserved PNA DESIGN

 

 

14 2021 NeuBase Therapeutics, Inc. All Rights Reserved PEPTIDE NUCLEIC ACIDS (PNA) N H 2 H N N H H N N H H N N H C O O H O O O O O R x R x R x R x R x O R x R x PROTEIN G T A N N H N H 2 N O O N N H N H N O O C O N H 2 O O O C C A O H O O O P O O O O O H P O O O - O O P O O O - O - H O H O H O H O T G PNA RNA

 

 

15 2021 NeuBase Therapeutics, Inc. All Rights Reserved PNA DS DNA BINDING • Nanomolar triplex affinity • >100x higher than DNA • Triplex >100x faster than invasion Hansen ME et al . Nucleic Acids Res . 2009;37(13):4498 - 4507

 

 

16 2021 NeuBase Therapeutics, Inc. All Rights Reserved PNA PROPERTIES: CHEMISTRY • Oligomers are synthesized by conventional solid phase peptide chemistry • Charge neutral, generally hydrophilic and water soluble • Chemically and biologically stable NH N B O O NH N NH B O O NH N B O O Egholm M et al . J Amer Chem Soc 1992 114 (5), 1895 - 1897; Christensen L et al . J Pept Sci . 1995;1(3):175 - 183; Demidov VV et al . Biochem Pharmacol . 1994;48(6):1310 - 1313

 

 

17 2021 NeuBase Therapeutics, Inc. All Rights Reserved IN VIVO ADMINISTRATION AND PK IV administration: t ½ 30min SC administration: t ½ 120min Brolin et al . Nucleic Acid Ther , 2020. doi : 10.1089/nat.2020.0856

 

 

18 2021 NeuBase Therapeutics, Inc. All Rights Reserved WHY PNA: ADVANTAGES • Exquisite biological and chemical stability • Robust and versatile chemistry • Multiple modes of action for a specific indication • Low inherent toxicity • Unique technology allowing profound medicinal chemistry modification without jeopardizing receptor affinity/specificity Functional backbone decoration Insert chemical functionality Insert chemical functionality

 

 

19 2021 NeuBase Therapeutics, Inc. All Rights Reserved PREVIOUS CHALLENGES • Cellular uptake/delivery • Pharmacokinetics • Formulation • Therapeutic window

 

 

20 2021 NeuBase Therapeutics, Inc. All Rights Reserved PATROL Δ IMPROVES 1 ST GEN PNA TO IMPART DRUG - LIKE PROPERTIES Scaffold Modifications Delivery Domains Base Modifications Tunable for RNA or DNA targets Tunable binding affinity ADME/Tox optimization Efficient intracellular delivery Tissue targeting ADME/Tox optimization Tunable specificity and affinity Tunable for RNA or DNA targets Optimize biophysical properties

 

 

21 2021 NeuBase Therapeutics, Inc. All Rights Reserved WHY • Newest improved chemistry • New delivery technology • Carefully selected indications & targets • Focused and scientific approach • Globally recognized experts • IP generation

 

 

MYOTONIC DYSTROPHY TYPE 1 (DM1)

 

 

23 2021 NeuBase Therapeutics, Inc. All Rights Reserved POTENTIAL TO BE BEST - IN - CLASS IN DM1 2022 on track for clinic 1 Functional rescue of myotonia in animal model Splice rescue in animal model Activity via subcutaneous and intravenous routes Whole - body solution designed to maintain DMPK levels 1 Calendar year 2021 Preclinical execution 1

 

 

24 2021 NeuBase Therapeutics, Inc. All Rights Reserved DM1 IS DEVASTATING WITH HIGH UNMET NEED DM1 is a dominantly inherited disease defined by a repeat expansion in the DMPK gene with severity defined by expansion size 3 1 out of 20,000 are affected by DM1 globally 4 Most patients have myotonia (impaired muscle relaxation), muscle weakness and wasting, cardiac conduction defects, cognitive deficits and decreased lifespan 1 70 - 80% of congenital onset patients require mechanical ventilation, with mortality rates between 15 - 20% 2 1 https://www.myotonic.org; 2 https://www.mda.org; 3 Mahadevan M et al. Science . 1992 Mar 6;255(5049):1253 - 5. 4 Bird TD. 1999 Sep 17 In: Adam MP et al ., editors. GeneReviews®; 1993 - 2021. Metrics are approximate. 0 currently approved therapies that alter the natural history of DM1

 

 

25 2021 NeuBase Therapeutics, Inc. All Rights Reserved Expanded CUG repeats in DMPK mRNA 3’ UTR form toxic hairpins in the nucleus DISEASE PATHOGENESIS • Hairpins form nuclear aggregates together with MBNL splice proteins • Results in widespread mis - splicing of pre - mRNAs • Produce altered proteins which are dysfunctional in adults DNA Sequestered splicing factors RNA Ribosome mRNA Pre - mRNA RNA polymerase Only wild - type DMPK is translated Mutant DMPK pre - mRNA in nuclear aggregates Adapted from Muangkaew and Vilaivan, Bioorg Med Chem Lett 2020; 30:127064

 

 

26 2021 NeuBase Therapeutics, Inc. All Rights Reserved THERAPY DESIGNED TO RESTORE CORRECT SPLICING • Therapy releases nuclear aggregates • Designed to maintain DMPK mRNA and allow translation of mutant transcript DMPK mRNA translated Nuclear aggregates released transcription Ribosome mRNA Pre - mRNA RNA polymerase DNA Free MBNL splicing factors RNA PNA Adapted from Muangkaew and Vilaivan, Bioorg Med Chem Lett 2020; 30:127064

 

 

27 2021 NeuBase Therapeutics, Inc. All Rights Reserved KEY ADVANCEMENTS TOWARD THE CLINIC December 2020: splice rescue in patient cells, while maintaining DMPK protein levels, and in vivo June 2021: functional rescue in vivo after systemic dosing • Reduce nuclear aggregates in muscle • Well tolerated at pharmacologically active doses • Rescue: • Splicing defects across many transcripts, including muscle chloride channel • Muscle chloride channel protein expression • Myotonia (3 mg/kg subcutaneous dose)

 

 

28 2021 NeuBase Therapeutics, Inc. All Rights Reserved Single Dose*, Day 21 Vehicle *29 mg/kg iv NUCLEAR INCLUSIONS ARE REDUCED IN HSA LR MUSCLE AFTER DOSING

 

 

29 2021 NeuBase Therapeutics, Inc. All Rights Reserved 0.0 0.2 0.4 0.6 0.8 1.0 Day 13 mDSI 1 MIS - SPLICING CORRECTED IN VIVO Single Dose administered IV at 29 mg/kg in the HSA LR mouse ~75% splice correction observed in tibialis anterior at ~ 2 weeks after single dose Clcn1 splice correction of myotonia - causing transcript ***p<0.0001 All mis - spliced transcripts Rescue of mis - splicing Untreated Treated Healthy 0

 

 

30 2021 NeuBase Therapeutics, Inc. All Rights Reserved SKELETAL MUSCLE CHLORIDE CHANNEL (CLCN1) IS RESTORED IN VIVO Single dose = 29mg/kg IV, western blotting from soleus muscle on day 20 after dosing Treated (channel restored) Clcn1 protein Beta - actin loading control Healthy (channel present) Untreated (channel reduced) FVB background unaffected strain HSA LR affected

 

 

31 2021 NeuBase Therapeutics, Inc. All Rights Reserved FUNCTIONAL RESCUE OF MYOTONIA IN VIVO 3mg/kg dosed weekly x4 in the HSA LR mouse Subcutaneous route of administration ~70% reduction of myotonia at 35 days post first - dose via plantar flexor torque assay 0.0 0.1 0.2 0.3 0.4 0.5 0.6 Time to Relaxation (s) *p<0.05 Healthy Treated Untreated

 

 

32 2021 NeuBase Therapeutics, Inc. All Rights Reserved KEY ADVANCEMENTS TOWARD THE CLINIC December 2020: splice rescue in patient cells, while maintaining DMPK protein levels, and in vivo June 2021: functional rescue in vivo after systemic dosing • Reduce nuclear aggregates in muscle • Well tolerated at pharmacologically active doses • Rescue: • Splicing defects across many transcripts, including muscle chloride channel • Muscle chloride channel protein expression • Myotonia (3 mg/kg subcutaneous dose)

 

 

33 2021 NeuBase Therapeutics, Inc. All Rights Reserved ON TRACK TO FIRST CLINICAL STUDY IN 2022 1 Ongoing PK/ADME Initiated CMC process research CLINIC Initiate non - clinical toxicology Pre - IND meeting 1 Calendar year

 

 

DR. ROBERT FRIEDLANDER

 

 

35 2021 NeuBase Therapeutics, Inc. All Rights Reserved ROBERT FRIEDLANDER, M.D., M.A. • Chairman, Walter E. Dandy Distinguished Professor, University of Pittsburgh Department of Neurological Surgery • Co - Director, UPMC Neurological Institute • Head, Cerebrovascular Neurosurgery • Director, Complex Brain Surgery Program Currently Previously • Professor, Harvard Medical School • Vice - Chairman of Neurosurgery, Associate Director of Cerebrovascular Surgery, and Co - Director of the Neuroscience Research Center at the Brigham and Women’s Hospital in Boston Honors & Awards • National Academy of Medicine • International Charcot Prize for Motor Neuron Diseases • Award from the Academy of Neurological Surgeons • H. Richard Winn Prize from the Society of Neurological Surgeons Associations • American Society for Clinical Investigation • Association of American Physicians • National Advisory Council of the National Institutes of Neurological Disorders and Stroke (NINDS)

 

 

HUNTINGTON’S DISEASE

 

 

37 2021 NeuBase Therapeutics, Inc. All Rights Reserved KEY ADVANCEMENTS Previously: selective mutant huntingtin protein knockdown in human patient cells June 2021: Subcutaneous dosing crosses BBB and selectively knocks down mutant huntingtin protein in the mouse brain • Knock - down achieved by targeting either RNA or DNA • Well tolerated at pharmacologically active doses

 

 

38 2021 NeuBase Therapeutics, Inc. All Rights Reserved HUNTINGTON’S DISEASE (HD) IS SEVERE & INCURABLE 100% of patients carry a repeat expansion in the huntingtin ( HTT ) gene 1 Long poly - glutamine tract in the protein cause cell death Progressive neurodegeneration movement disorder, mood disturbances, cognitive impairment and a whole - body disorder 0 approved disease modifying therapies 15 - 20 years is life expectancy after diagnosis 2 1 Pringsheim T et al. Mov Disord . 2012 Aug;27(9):1083 - 91; 2 Solberg OK et al . J Huntington’s Disease 2018; 7(1): 77 - 86. 3 Yohrling G et al . Neurology . April 14, 2020; 94. 4 https://rarediseases.org. Metrics are approximate. 41,000 HD cases in the US alone 3 >200,000 at risk from the disease in the US alone 4

 

 

39 2021 NeuBase Therapeutics, Inc. All Rights Reserved Unaffected HD Patient Harper PS. Huntington’s disease . London: W.B. Saunders, 1991 PRIMARILY KNOWN AS A PROGRESSIVE CNS DISEASE • Neuronal loss starts in the striatum and progresses to the cortex

 

 

40 2021 NeuBase Therapeutics, Inc. All Rights Reserved • Weight loss • Muscle atrophy • Glucose intolerance • Osteoporosis • Testicular atrophy • Heart failure • Cardiac abnormalities Systemic administration of PATrOL ǝ has the potential to be a whole - body solution Pros: Reaches all organs, easy to administer, low risk, low training requirement HD IS ALSO A WHOLE - BODY DISEASE

 

 

41 2021 NeuBase Therapeutics, Inc. All Rights Reserved NORMAL HUNTINGTIN IS WIDELY EXPRESSED AND IMPORTANT FOR: • Cell signaling, transcriptional regulation, molecular trafficking, axonal transport • Modulating brain - derived neurotrophic factor (BDNF) production • Mitochondrial function • Caspase inhibition • Homozygous gene knock - out is embryonic lethal in mice • Hemizygous mice demonstrate neurodegeneration in subthalamic nucleus and globus pallidus • Postnatal protein reduction is detrimental LOSS OF NORMAL HUNTINGTIN IN ANIMAL MODELS IS DETRIMENTAL

 

 

42 2021 NeuBase Therapeutics, Inc. All Rights Reserved SYSTEMIC DOSING ENABLES A WHOLE - BODY SOLUTION Untreated Intrathecal Intrastriatal Systemic no drug drug

 

 

43 2021 NeuBase Therapeutics, Inc. All Rights Reserved SIZE DIFFERENCES BETWEEN MOUSE AND HUMAN BRAIN • Makes clinical translation of intrathecal administration results difficult

 

 

44 2021 NeuBase Therapeutics, Inc. All Rights Reserved ALLELE - SELECTIVE KNOCK - DOWN IS IMPORTANT • Maintenance of normal huntingtin function while eliminating toxic protein is ideal

 

 

45 2021 NeuBase Therapeutics, Inc. All Rights Reserved DNA PNA CAG repeats RNA Ribosome transcription mRNA RNA polymerase SUBCUTANEOUS DOSING CROSSES BBB AND KNOCKS DOWN MUTANT HUNTINGTIN PROTEIN IN THE MOUSE BRAIN 1 1 zQ175 mouse model with 190 CAG repeats in exon 1 of HTT ; 60 mg/kg subcutaneous dose day 1 & 4; sacrifice day 7 0 20 40 60 80 100 120 Relative HTT protein expression (%) NS untreated treated mHTT wtHTT *p<0.05 Adapted from Muangkaew and Vilaivan , Bioorg Med Chem Lett 2020; 30:127064 ENGAGING THE TRANSCRIPT

 

 

46 2021 NeuBase Therapeutics, Inc. All Rights Reserved DNA PNA CAG repeats RNA Ribosome transcription mRNA RNA polymerase 0 20 40 60 80 100 120 Relative HTT Protein Expression (%) untreated treated mHTT wtHTT *p<0.05 ENGAGING THE GENOME SUBCUTANEOUS DOSING CROSSES BBB AND KNOCKS DOWN MUTANT HUNTINGTIN PROTEIN IN THE MOUSE BRAIN 1 1 zQ175 mouse model with 190 CAG repeats in exon 1 of HTT ; 30 mg/kg subcutaneous dose day 1 & 4; sacrifice day 7 Adapted from Muangkaew and Vilaivan , Bioorg Med Chem Lett 2020; 30:127064

 

 

47 2021 NeuBase Therapeutics, Inc. All Rights Reserved KEY ADVANCEMENTS Previously: selective mutant huntingtin protein knockdown in human patient cells June 2021: Subcutaneous dosing crosses BBB and selectively knocks down mutant huntingtin protein in the mouse brain • Knock - down achieved by targeting either RNA or DNA • Well tolerated at pharmacologically active doses

 

 

48 2021 NeuBase Therapeutics, Inc. All Rights Reserved Systemic dosing for CNS and whole - body solution Patient – friendly subcutaneous route HD PROGRAM: THE PATH FORWARD In vivo translational profiling Optimization of delivery and target engagement

 

 

KRAS G12D & G12V MUTATIONS IN ONCOLOGY

 

 

50 2021 NeuBase Therapeutics, Inc. All Rights Reserved MUTATIONS IN THE RAS GENE FAMILY CAUSE 30% OF ALL CANCERS Our compounds targeting KRAS codon 12 mutations have potential to work against NRAS and HRAS RAS - driven cancers are common, severe and largely untreatable KRAS mutations are the most common RAS mutations 1 Normal KRAS protein is essential for normal function G12D and G12V account for ~55% of all KRAS mutations 1 Papke B et al . ACS Pharmacology & Translational Science . 2021. Metrics are approximate.

 

 

51 2021 NeuBase Therapeutics, Inc. All Rights Reserved approved therapies for the 2 most prevalent RAS mutations https://www.cancer.gov/research/key - initiatives/ras/about

 

 

52 2021 NeuBase Therapeutics, Inc. All Rights Reserved KEY ADVANCEMENTS • New program initiated in 2021 • Allele - selective target engagement of KRAS G12D and G12V • Target engagement of the genome and the transcriptome • Tumor growth inhibition after intra - tumoral administration • Reduction of downstream signaling validates target engagement

 

 

53 2021 NeuBase Therapeutics, Inc. All Rights Reserved RNA TARGETING OF KRAS Ribosome mRNA transcription Pre - mRNA RNA polymerase DNA PNA RNA Adapted from Muangkaew and Vilaivan , Bioorg Med Chem Lett 2020; 30:127064 • Engaging RNA to inhibit translation

 

 

54 2021 NeuBase Therapeutics, Inc. All Rights Reserved 0 200 400 600 800 1000 1200 1400 1600 1800 0 5 10 15 20 25 Tumor Volume (mm³) Day IN VIVO TUMOR GROWTH INHIBITION VIA RNA TARGETING OF G12D MUTATION * * * Post - treatment durability treated untreated G12D is the most prevalent mutation 1 accounting for 33% of KRAS mutations in patients Inhibition of tumor growth after 0.3 mg/kg intra - tumoral injections into HPAFII heterozygous pancreatic cancer xenografts 8 days after first dose until statistically significant growth inhibition achieved Dose 2 Dose 1 Dose 3 n=6 animals per group, *p<0.05 1 Papke B et al . ACS Pharmacology & Translational Science . 2021

 

 

55 2021 NeuBase Therapeutics, Inc. All Rights Reserved 0 20000 40000 60000 80000 100000 120000 140000 160000 180000 CREB 0 20000 40000 60000 80000 100000 120000 140000 MEK Ras CRaf BRaf Raf MEK ERK p90RSK ERK RSK3 MSK1 CREB P P P P P P P P P P P P P P 0 20000 40000 60000 80000 100000 120000 140000 160000 RSK3 0 20000 40000 60000 80000 100000 120000 140000 ERK IN VIVO MUTANT KRAS KNOCK - DOWN DECREASES DOWNSTREAM SIGNALING Reduction in phosphorylation levels of multiple pathway members in oncogenic cascade Total protein normalized intensity Total protein normalized intensity Total protein normalized intensity Total protein normalized intensity treated untreated

 

 

56 2021 NeuBase Therapeutics, Inc. All Rights Reserved IN VIVO TUMOR GROWTH INHIBITION VIA RNA TARGETING OF G12V MUTATION 0 100 200 300 400 500 600 700 0 10 20 30 40 50 60 70 Tumor Volume (mm³) Day G12V is the second most prevalent mutation 1 accounting for 23% of KRAS mutations in patients Inhibition of tumor growth after 0.3 mg/kg intra - tumoral injections into CAPAN - 2 heterozygous pancreatic cancer xenografts 3 doses leads to prolonged tumor growth inhibition treated untreated 1 Papke B et al . ACS Pharmacology & Translational Science . 2021 n=6 animals per group Dose 2 Dose 1 Dose 3

 

 

57 2021 NeuBase Therapeutics, Inc. All Rights Reserved DNA TARGETING OF KRAS RNA polymerase DNA PNA RNA Ribosome mRNA transcription Pre - mRNA Adapted from Muangkaew and Vilaivan, Bioorg Med Chem Lett 2020; 30:127064 • Engaging DNA to inhibit transcription

 

 

58 2021 NeuBase Therapeutics, Inc. All Rights Reserved 0 0.2 0.4 0.6 0.8 1 1.2 SELECTIVITY FOR G12D RAS PROTEIN KNOCK - DOWN VIA DNA TARGETING • Evidence for invasion of dsDNA in vitro • Inhibition of transcription of mutant allele • ~90% of mutant protein knockdown relative to wild - type *** = p<0.001 Compound X Compound Y G12D mutant RAS Wild - type RAS Normalized protein levels *** = p<0.001

 

 

59 2021 NeuBase Therapeutics, Inc. All Rights Reserved KEY ADVANCEMENTS • New program initiated in 2021 • Allele - selective target engagement of KRAS G12D and G12V • Target engagement of the genome and the transcriptome • Tumor growth inhibition after intra - tumoral administration • Reduction of downstream signaling validates target engagement

 

 

60 2021 NeuBase Therapeutics, Inc. All Rights Reserved KRAS PROGRAM: THE PATH FORWARD In vivo translational profiling Select target tumor types Power towards the clinic Optimization of tumor delivery & target engagement