Corporate Overview

O C T O B E R 2 0 2 1

This presentation contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this presentation, including statements regarding the benefits and capabilities of our transcriptome panel and the timing of its commercial launch, possible companion diagnostic and HTG Molecular Diagnostics, Inc. (“HTG”) diagnostic products, potential addressable markets and the size of those markets, including new markets and opportunities expected as a result of our full transcriptome technology, HTG being well positioned in the emerging field of RNA therapeutics, our timeline strategy, planned product development and our product and technology roadmap, prospects, and plans and objectives are forward-looking statements. The words ‘‘anticipate,’’ ‘‘believe,’’ ‘‘estimate,’’ ‘‘expect,’’ ‘‘intend,’’ ‘‘may,’’ ‘‘plan,’’ ‘‘predict,’’ ‘‘project,’’ ‘‘target,’’ ‘‘potential,’’ ‘‘will,’’ ‘‘would,’’ ‘‘could,’’ ‘‘should,’’ ‘‘continue,’’ and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in forward-looking statements, including due to risks and uncertainties associated with the development and commercialization of products, competition with new and existing technologies, the outcome of relationships with third parties, the COVID-19 pandemic and other factors as discussed under the heading “Risk Factors” in our quarterly report on Form 10-Q for the quarter ended June 30, 2021, as filed with the Securities and Exchange Commission. The forward-looking statements contained in this presentation reflect our views with respect to future events as of the date set forth on the first page of this presentation, and we assume no obligation to update any forward-looking statements as a result of new information, future events or otherwise as of such date.

This presentation also contains estimates, projections and other information concerning our industry, our business, and the markets for our products, product candidates and services, as well as data regarding market research, estimates and forecasts prepared by our management. Information that is based on estimates, forecasts, projections, market research or similar methodologies is inherently subject to uncertainties and actual events or circumstances may differ materially from events and circumstances reflected in this information. These statements are based upon information available to us as of the date of the presentation, and while we believe such information forms a reasonable basis for such statements, such information may be limited or incomplete, and our statements should not be read to indicate that we have conducted an exhaustive inquiry into, or review of, all potentially available relevant information. These statements are inherently uncertain, and you are cautioned not to unduly rely upon these statements

Forward-looking Statements

P R O P R I E T A R Y A N D C O N F I D E N T I A L2

P R O P R I E T A R Y A N D C O N F I D E N T I A L3

HTG is accelerating precision medicine - from diagnosis to treatment - by harnessing the power of transcriptome-wide profiling to drive translational research, clinical diagnostics andtargeted therapeutics across a variety of disease areas.

Building on more than a decade of pioneering innovation and partnerships with biopharma leaders and major academic institutes, HTG’s proprietary RNA platform technologies are designed to make the development of life science tools and diagnostics more effective and efficient and to unlock a differentiated and disruptive approach to transformative drug discovery.

P R O P R I E T A R Y A N D C O N F I D E N T I A L4

H T G M O L E C U L A R H T G T H E R A P E U T I C S

P R E C I S I O N M E D I C I N E

RNAdiagnostic services/tools RNA-targeted small molecule

drug discovery

The Power of RNA and Gene Expression Profiling (GEP) in Precision Medicine

P R O P R I E T A R Y A N D C O N F I D E N T I A L5

RNA

Transcriptome

DNA Protein

Proteome

Making PrecisionMedicine More Precise

MH S V I D

Genome

RNA is what is happening Proteins are the working molecules …but are very difficult to multiplexDNA represents the blueprint

Mutations are a powerful element of precision medicine but many patients

do not have an actionable mutation

In many disease areas, DNA

mutations are not relevant to disease

Pathway and gene analysis are excellent

biomarkers to understand disease and mechanism of

action (MOA)

Transcript abundance is often superior to

protein analysis, and easier

to multiplex

Protein analysis represents the gold

standard of understanding what is happening biologically

Structure and multiplexing are two significant

barriers inhibiting protein analysis

What Differentiates HTG for RNA Analysis?

P R O P R I E T A R Y A N D C O N F I D E N T I A L6

Faster…easier…higher expected success rate…lower sample requirement

INCREASED SENSITIVITY SIMPLIFIED WORKFLOW CUTTING-EDGE PERFORMANCE

• 5-10x less starting sample required

• Compatible with both liquid andtissue samples

• Maintain effectiveness with degraded samples

• Avoids complex and biased RNA-seq workflow steps

• Turn-around time of 3 days vs.7 days or more

• Bioinformatics in <1 hour vs.4-8 hours or more

• Excellent concordance with RNASeqand synthetic RNA spike in controls

• High assay success rate and large dynamic range

• High-plex (up to 20K) panels, including whole transcriptome mRNA and miRNA panels

Core Business – Gene Expression Profiling (GEP) in Three Segments

P R O P R I E T A R Y A N D C O N F I D E N T I A L7

Proprietary technology platform for NGS RNA gene-expression profiling (GEP)serving the full precision medicine value-chain

TRANSLATIONAL PROFILING

NGS GEP publications have doubled to >10K annually over

the last 5 years, immuno-oncology is a major driver

DRUG DEVELOPMENT

Leading biopharma customers using RNA biomarkers to drive

development of potential targeted therapies

CLINICAL DIAGNOSTICS

MDx companies are conducting massively scaled NGS GEP for

new test R&D and major cancer centers are building LDT’s

Data analysisSequencingLibrary prep

EDGESeq Workflow

P R O P R I E T A R Y A N D C O N F I D E N T I A L8

Low Sample Input No RNA / DNA Extraction Simplified Sequencing and Bioinformatics

Sequencer AgnosticIllumina

Thermo Fisher Scientific

HTG Reveal Data Analysis Suite

Sample prep

Patented andProprietary Chemistry

Core Business – RNA GEP Market Remains Large and Fast Growing

P R O P R I E T A R Y A N D C O N F I D E N T I A L9

2015 2020 2025F

CAGR in GEP tools supplier market15%

$0.5B

$1.0B

$2.0BMARKET SIZE

Source - DeciBio

Core Business – Seeing Recovery in Key Metrics

P R O P R I E T A R Y A N D C O N F I D E N T I A L10

2019 2020 YTD Q1 Q2 Q3 Q4 Q1 Q2

$2.0M$1.7M $1.7M

$2.5M

$1.4M

$2.1M

2020 2021

REVENUE

88

44

63

PHARMA PROGRAMS

Revenue is direct revenue from products and product related services

Momentum in Publications Referencing EdgeSeq

P R O P R I E T A R Y A N D C O N F I D E N T I A L11

2015 2016 2017 2018 2019 2020 2021

CUMULATIVE

2046

88

131

182

266

318

P R O P R I E T A R Y A N D C O N F I D E N T I A L12

Provides the mRNA transcriptome with the same value proposition as previous EdgeSeq targeted panels

• Smaller sample load• High success rate with FFPE• Simpler workflow• Faster turnaround time• Easy bioinformatics

Helping to enable the next round of growth

HTG’s new human mRNA transcriptome product, approximately 20,000 genes

P R O P R I E T A R Y A N D C O N F I D E N T I A L13

HTG Transcriptome Panel (HTP) White Papers

White paper # 1(November 2020) demonstrated equivalency to RNASeq

White paper # 2(February 2021) demonstrated superiority to RNASeq

White paper # 3(August 2021) demonstrated final assay configuration superiority to RNASeqand data integration into REVEAL software

ASSAY PASS RATE AND SAMPLE REQUIREMENTS vs RNASeq

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Technical Highlights – HTP System Performance

* Only 1 sample required 2 sections** RNA-Seq samples failed to generate sufficient extracted RNA to process samples.

HTG works with smaller samples, is less sensitive to sample age, has a faster turnaround timeand has a higher sample success rate than RNASeq

Comparison of HTG and RNA-Seq Platforms

HTG Panel RNA-Seq

Number of FFPE Slides Used 1-2 * 4-8

Sample Type Used FFPE(extraction-free)

FFPE(extracted RNA)

Overall Pass Rate 100% (24/24) 75% (18/24) **

Pass Rate for Samples Older than 10 years 100% (13/13) 63% (7/11)

Turn-Around Time 3 days 7 days

Sample Information

Cancer indication

Age of FFPE Block

Number of Blocks

Met RNA-Seq Input Requirement

Breast<5 years 2 2/2

>10 years 2 2/2

Prostate<5 years 2 2/2

>10 years 2 0/2

Lung<5 years 3 2/3

>10 years 2 0/2

Colorectal<5 years 3 3/3

>10 years 3 3/3

Melanoma<5 years 3 2/3

>10 years 2 2/2

HTG SHOWS HIGH ACCURACY vs SPIKED IN CONTROLS AND IS CONCORDANT WITH RNASeq

15

Technical Highlights – HTP Accuracy

Comparison of differential expression analysis results between the HTG panel and RNA-Seq for a representative set of breast and colorectal cancer FFPE samples. Log fold change values for RNA-Seq are plotted on the y-axis and log fold change values for the HTG panel are plotted on the x-axis. Blue dotted line is the unity line

Assay linearity and dynamic range using spiked-in ERCC transcripts. The predicted amount of log2 ERCC spike-in (X-axis) were correlated with the log2 transformed signal generated by the ERCC transcripts (Y-axis). Pearson correlation coefficients are in the upper left-hand corner of each plot.

Revenue Q2 Actual

$190K

HTP Commercialization Update

P R O P R I E T A R Y A N D C O N F I D E N T I A L16

EARLY ADOPTER PROGRAM

EAP Agreements• 18 fully signed (7 US / 11 EU)

• 28 in negotiation (11 US / 17 EU)

Project Status• 7 SOW complete – in process in Tucson

• 5 kits shipped – in process @ Customer

• 6 pending final SOW completed

MARKETING UPDATE

CompletedInitial Mailing Campaign

PlannedMultiple Targeted Campaigns

Banner Ads inGenomeWeb, LabRoots & GEN

Market Opportunities

P R O P R I E T A R Y A N D C O N F I D E N T I A L17

MAJOR DXCONTENT PROVIDERS*

MAJOR CANCER CENTERSIN THE US AND EUROPE

72 NCI centers in the US

42 OECI centers in Europe

Source – Cancer.gov, OECI.eu

* Examples of potential customers

FINANCING

PROPRIETARY TECHNOLOGY

CUSTOMERS/DISTRIBUTION

A Decade of Innovation at HTG

P R O P R I E T A R Y A N D C O N F I D E N T I A L18

2021201920172015<2013

JULY 2021

Drug Discovery Business

Unit Created

Whole transcriptome mRNA panel

EpiEdge Seq feasibility

Immuneresponse panel

MousemRNA panel

Immunooncology panel

Pan B-cell lymphoma

panel

Whole transcriptome miRNA panel

U.S. PatentNo. 8,741,564 -

June 3, 2014

Oncologybiomarker

panel

PDP 1 agreement

PDP 3agreement

Merck KGaACDx agreement

QIAGEN PDPCDx agreement

PDP 2agreement

QIAGENdistribution agreement

IPO Follow on financing

2nd follow on financing

DLBCL COO panel

RNA profiling:

Advanced MedicinalChemistry Platform

mRNA Transcriptome Epitranscriptome Novel RNA

Drug Discovery and Development Platform

Novel Drug Discovery, a Natural Extension of Our Business

P R O P R I E T A R Y A N D C O N F I D E N T I A L19

Leveragingour heritage

Adding new technology platforms

Enabling a powerful new capability

Targeted RNAtranscriptomic profiling:

RNA Opens Up Huge New Universe of Drug Targets

P R O P R I E T A R Y A N D C O N F I D E N T I A L20

TODAY’S PROTEIN PARADIGM(After 100 years of drug discovery)

POTENTIAL WITH RNA

~70%Non-coding

Non-diseaserelated 1.5%

~30%

Nature Reviews, August 2018

Could bedruggableas mRNA

Proteins(1.5%)

20x increase in new targets

~20,000coding genes

~1,000targeted by existing drugs

HumanGenome(100%)

48%

25%

21%

3% 3%

Two Big Problems in Clinical Development Persist: Efficacy & Safety

P R O P R I E T A R Y A N D C O N F I D E N T I A L21

55%

14%

14%

7%

10%• <12% of drugs entering clinical trials succeed*

• Approx $985M per drug approved*

* pharma.org

… we plan to improve on both.

REASON FOR FAILURE

PHASE

IIPHASE

III

69%73%

EfficacySafetyStrategyOperationalCommercial

OUR SOLUTION

The Value of Early Pre-clinical Insight

P R O P R I E T A R Y A N D C O N F I D E N T I A L22

Used too latein process

ClinicalTranscriptomic

profiling

Few levers:• Dosing• Post-facto patient selection

TODAY

Use early,during small moleculediscovery and design

PreclinicalFull system

transcriptomicprofiling

Medicinalchemistry

Many levers:• MOA / biology• Which patients respond → patient selection• Which pathways are activated → off-target effects

OPPORTUNITY

P R O P R I E T A R Y A N D C O N F I D E N T I A L23

Literature concurs that integrating big data expression profiling can improve therapeutic candidates

Early and often transcriptome profiling can disrupt drug development

Innovative Proprietary Technology

HTG Epi-EdgeSeq

Epitranscriptome

mRNA transcriptome

miRNA transcriptome

EdgeSeq

Assembling A Drug Discovery and CDx Powerhouse

P R O P R I E T A R Y A N D C O N F I D E N T I A L24

Nervous System Disease Cardiovascular

Diabetes

Liver Disease ImmunoOncology

Rare Disease

Infectious DiseaseImmunology

Genetic Disease Metabolic Disease

Disease state agnostic:

Precision Therapeutics

Patented Molecules

CompanionDiagnostics

and

HTG InformaticsInformatics

HTG ChemistryMachine learning

driven small molecule chemistry

Chemistry Platform

IP Strategy

P R O P R I E T A R Y A N D C O N F I D E N T I A L25

Epi-Transcriptome

miRNATranscriptome

mRNA Transcriptome

Our Comprehensive RNA ProfilingPlatform Technology

Enablingsimultaneous mRNA, miRNA and RNAmodification analysis

NEW

NEW

Ability to generate

~42,000data points from every

sample

Not All Transcriptome Profiling is Created Equal

P R O P R I E T A R Y A N D C O N F I D E N T I A L26

Generic Technology

OTHERS

Proprietary Technology

Powerful chemistry that uses less sample, is more robust and

is easier to use

Powerful technology but requiresa lot of very pure RNA and a

sophisticated workflow

ADVANTAGES

Large sample quantities required Increased Sensitivity 5-10x less starting sample required

1-2 week turnaround if a biostatistician is on-site Simplified Workflow 3 day turnaround

63%-75% assay success rate Cutting Edge Performance 96%+ assay success rate*

EdgeSeqTraditional RNA-Seq

*Source – Actual HTG internal service lab performance

Multiple Target Strategies for Drug Discovery Differentiates Us

P R O P R I E T A R Y A N D C O N F I D E N T I A L27

Target Agnostic ApproachRMP* Target Focused Approach

EdgeSeq –RMP panel informs efficacy• Potential for patient

stratification

• Abundance of transcriptome mods

RNA Target Focused Approach

EdgeSeq –on/off target profiles

EdgeSeq Published• Transcripts• Modifications

Preferred Profile Signatures• Tumorigenesis• Fibrosis• Neurodegeneration• Rare disease• Other

Proprietary

*RMP = RNA Modifying Proteins

THE PLATFORM THE BENEFITS

P R O P R I E T A R Y A N D C O N F I D E N T I A L28

Advanced Medicinal Chemistry, Powered by Machine Learning

Predictive Models to Accelerate Process

Multiple paths to design a multi-parameter optimization approach that maximizes the

probabilityof success.

Innovative Chemical Library Design

Advances in Chemical Space creation make it possible to

create novel compounds that can form the same types of

interactions with known RNA binding small molecules.

Data Driven Approachto Optimization

Analyzing historical data to optimize and update relevant

parameters creates an iterative approach to the entire process.

Streamlining DiscoveryThen Now

Rapid:Days – weeks

LibraryDesign

Lengthy:Months – years

Targeted:~150

compounds

#Compounds

Chaotic:~500,000

compounds

Easierto screen

and iterate

Harderto screen

and iterate

HTG Positioned for High Value-add throughout The Process

P R O P R I E T A R Y A N D C O N F I D E N T I A L29

DRUG DISCOVERY CDx DEVELOPMENT

NIH / Academia

profiling tools

Iterative Process

Potential royalties and

milestones or asset sale

Development candidate

out licensed or soldby HTG

CDx Development

TargetDiscovery Validation Library

DesignCell-basedScreening Hit to Lead

1 2 3 4 5Pre-IND Phase 1 Phase 2 Phase 3 Launch

1 2 3 4 5

Potential CDxrevenues

Approval

profiling tools

• Analyze disease vs normal with mRNA, miRNA, m6A and other modifications.

• Map disease states

• Identify potential targets

• Knock on/knock off

• CRISPR

• Target validation

• Profiling

• Pharmacophore, structure and ligand based structures

• Binding site assessments

• In silico screening

• Targets are screened with targeted libraries to identify hits

• Transcriptomic profiling to assess efficacy (return to normal) and tox and other off target effects

• Structure optimization

• Continued transcriptomic profiling to optimize efficacy

Target Discovery Validation Library Design Cell-based Screening Hit to Lead

1 2 3 4 5

HTG Drug Discovery Process – A Deeper Dive

P R O P R I E T A R Y A N D C O N F I D E N T I A L30

HTG Iterative Process

Developmentcandidate

HTG Iterative Process

HTG CDx Process – A Deeper Dive

P R O P R I E T A R Y A N D C O N F I D E N T I A L31

• Analyze disease vs normal with mRNA, miRNA, m6A and other modifications.

• Confirm mechanism

• Screen for off target and toxicity

• Using EdgeSeq profiling platform identify responder/non responders of patients via pathway analysis and sub-typing

• Confirm sub-type and/or pathway response and confirm biomarker strategy to accelerate drug development and registration

• Build IUO CDx

• Expand sub-types and indications to maximize market potential

• Expand CDx label

• Initiate commercialization seeking 1st line approval based on superior efficacy and lower toxicity

Pre-IND Phase 1 Phase 2 Phase 3 Launch

1 2 3 4 5

Approval

ONCOLOGY CLINICAL TRIALS LEVERAGING GEP REVENUE OPPORTUNITY FOR A CDx

P R O P R I E T A R Y A N D C O N F I D E N T I A L32

Significant Opportunity for Companion Diagnostics

Approved CDx

One front line CDx in a100k incidence rate cancer represents a potential$30M/yr revenue opportunity(assuming $300/test AUP)

3.1K

9%

2014

13%

2015

10% 15%

2016 2017 2019

18%

2018

20%

2.4K2.7K 2.9K

3.3K 3.4K 7%

3%

CAGROther oncology trials

Trials leveraging GEP*

Notes: * Only oncology (hematological and solid tumors) interventional trials measuring at least one drug (devices and surgery excluded), all sponsor types, with and without RNA / Gene expression biomarkersSource: Amplion; Contract Consultants

25%

Only ~50% of patients typically have actionable DNA mutation

Disease Area Drug ProgramRNA Targeted

MechanismTarget

DiscoveryTarget

Identification

Machine Learning Library

ConstructionCell Based Screening

Hit to Lead /Lead

Optimization

Oncology

Target 1 RMP

Target 2 RMP

Target 3 RMP

Target 4 Transcript Stability

Target 5 Multiple

Auto Immune Target 1 RMP

CNS Target 1 TBD

Rare Disease Target 1 TBD

Drug Discovery Pipeline

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Potential for 1st licensable

pre-INDasset by early

2023

In-license/public libraries

HTG CRO HTGSTRATEGY:

CHEM

ISTR

Y PL

ATFO

RM

Advanced

Classical

IntegratedGeneric

Differentiated from Traditional and Disruptive Competitors

P R O P R I E T A R Y A N D C O N F I D E N T I A L34

TARG

ET S

TRAT

EGIE

S

Novel

Validated

IntegratedGeneric

TRANSCRIPTOMIC PROFILING TECHNOLOGY TRANSCRIPTOMIC PROFILING TECHNOLOGY

TRADITIONAL RNA LANDSCAPE DISRUPTOR LANDSCAPE

Proven Team with Rich, Relevant Expertise

P R O P R I E T A R Y A N D C O N F I D E N T I A L35

Steve BaratSVP of Therapeutics

Marian NavratilSVP Research andDevelopment

Todd HuffmanVP of Strategy

Carl KaubVP of Chemistry

Des RaittVP of Business Development

Debra ThompsonPrincipal, Scientific Innovation

EXPERTISE

RNA profiling

Medicinal chemistry

Molecule design

Target /pipeline strategy

Licensing strategy

[image]

S6THERAPEUTICS

P R O P R I E T A R Y A N D C O N F I D E N T I A L36

THERAPEUTICS

Deep expertise in RNA translational profiling• To understand mechanism of disease

Ability to unlock massive drug discovery potential• 20x increase in druggable targets

Disrupting the paradigm by moving earlier in the process• Improving efficacy/safety; reducing current 90% clinical failure

Highly differentiated in RNA drug discovery space• Comprehensive proprietary profiling and medicinal chemistry

Capturing significant value-add potential and control• Evolution from service provider to service provider and drug discovery / CDx developer

Summary

P R O P R I E T A R Y A N D C O N F I D E N T I A L37

H T G M O L E C U L A R

Life science tools and diagnostics based on proprietary transcriptomic

technologies and informatics

H T G T H E R A P E U T I C S

Therapeutic discovery integrating transcriptomic profiling and machine learning guided library construction

Leading transcriptomics company developing profiling diagnostics andnovel drug candidates to determine the right therapy for the right patient