Form: 8-K

Current report filing

May 28, 2014

Documents

Corporate Presentation
May 2014
 
 
 
Forward Looking Statements
This presentation includes statements that are, or may be deemed, ‘‘forward-looking statements.’’ In some cases, these forward-looking
statements can be identified by the use of forward-looking terminology, including the terms “believes,” “estimates,” “anticipates,”
“expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should,” “approximately” or, in each case, their negative or other variations
thereon or comparable terminology, although not all forward-looking statements contain these words. They appear in a number of
places throughout this presentation and include statements regarding our intentions, beliefs, projections, outlook, analyses or current
expectations concerning, among other things, our ongoing and planned discovery and development of drugs targeting cancer stem
cells, the strength and breadth of our intellectual property, our ongoing and planned preclinical studies and clinical trials, the timing of
and our ability to make regulatory filings and obtain and maintain regulatory approvals for our product candidates, our ability to partner
our product development, the degree of clinical utility of our products, particularly in specific patient populations, expectations regarding
clinical trial data, our results of operations, financial condition, liquidity, prospects, growth and strategies, the length of time that we will
be able to continue to fund our operating expenses and capital expenditures, our expected financing needs and sources of financing,
the industry in which we operate and the trends that may affect the industry or us.  
By their nature, forward-looking statements involve risks and uncertainties because they relate to events, competitive dynamics, and
healthcare, regulatory and scientific developments and depend on the economic circumstances that may or may not occur in the future
or may occur on longer or shorter timelines than anticipated. Although we believe that we have a reasonable basis for each forward-
looking statement contained in this presentation, we caution you that forward-looking statements are not guarantees of future
performance and that our actual results of operations, financial condition and liquidity, and the development of the industry in which we
operate may differ materially from the forward-looking statements contained in this presentation as a result of, among other factors, the
factors referenced in the “Risk Factors” section of our Annual Report on Form 10-K for the year ended December 31, 2013 and our
quarterly report on Form 10-Q for the quarter ended March 31, 2014 (collectively, our “SEC Filings”). In addition, even if our results of
operations, financial condition and liquidity, and the development of the industry in which we operate are consistent with the forward-
looking statements contained in this presentation, they may not be predictive of results or developments in future periods. Any forward-
looking statements that we make in this presentation speak only as of the date of such statement, and we undertake no obligation to
update such statements to reflect events or circumstances after the date of this presentation, except as required by law.
You should read carefully our “Special Cautionary Notice Regarding Forward-Looking Statements” and the factors described in the
“Risk Factors” sections of our SEC Filings to better understand the risks and uncertainties inherent in our business.
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Investor Highlights
4
Ø Transformative, differentiated immunotherapy platform generating
 diverse pipeline with strong patent estate
Ø Promising monotherapy clinical data in lung cancer with impressive
 survival results
Ø 2 clinical development programs advancing into Phase 2 studies in
 2014 expected to generate key near-term catalysts
Ø Robust business development initiative with potential for multiple
 regional and global partnering opportunities
Ø Experienced team with extensive oncology operational, scientific,
 clinical and business development expertise
 
 
 
Management Team with Proven Track Record
5
Jeff Wolf  
Founder and CEO
•   Founder and managing director of Seed-One Ventures
•   Co-founder and director, Avigen
•   Co-founder and Chairman, TyRx Pharma
•   Founder and CEO, EluSys Therapeutics
Matt Czajkowski  
Chief Financial Officer
•   Fifteen years experience as Chief Financial Officer for a
    variety of early stage and public companies: Pozen, Inc., AAI
    Pharma, Incventure funded private companies
•   Chief Executive Officer of NextRay, Inc.
•   Investment Banker, Goldman Sachs & Co.’s Asia Pacific
    Mergers and Acquisition Group in Tokyo, Japan.
Anil K. Goyal, Ph.D., 
VP, Business Development
•   20 years of experience at private and public biotechnology
    companies covering all aspects of licensing, deal making,
    and strategic alliances
•   Management and BD roles with Serenex, Inc.,  Millennium
    Pharmaceuticals, Genome Therapeutics Corporation,
    Qualiber, and Ascletis Pharmaceuticals.
Melissa Price, Ph.D.  
VP, Clinical and Reg. Affairs
•   Led numerous oncology programs in both the biotech arena
    and the CRO space  
•   Leadership roles at INC Research, Novaquest, (a Quintiles
    Company and Attenuon
•   Published in numerous scientific journals
Taylor Schreiber, M.D., Ph.D.
VP, Research and Development
•   Co-inventor of significant elements of ImPACT technology
    platform
•   Co-inventor of TNFRSF25 agonist technology
•   Author of numerous immunology and heat shock protein-based
    cancer immunotherapy publications
•   Post-doctoral fellowship with Eckhard R. Podack, M.D., Ph.D., at
    University of Miami
 
 
 
World Renowned Advisory Boards
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Scientific Advisory Board
Clinical Advisory Board
 
 
 
Diverse Pipeline with Multiple Registration Opportunities
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From drug discovery to late-stage clinical development
 
 
 
IP Estate with Broad and Early Filings

Broad Issued Patents on ImPACT Platform & Pipeline
ImPACT Platform Technology
l   US and foreign patents issued for ImPACT technology for the treatment of cancer
     and viral disease
l   Additional patents on proprietary cell lines and clinical data
Worldwide Filings
l   Over 50 patent applications across 5 patent families
l   Enforceable patents issued in 15 countries and counting
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Heat’s ImPACT Therapy
Living Drug Factories
Antigen and adjuvant delivery in a single package
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Introducing gp96 — Immune System’s “Swiss Army Knife”*
“Molecular Warning System”
* Schild, H. & Rammensee, H. Gp-96 - The Immune System’s Swiss Army Knife. Nature Immunology 2, 100
 -101 (2000)
gp96
antigen
leash
l Natural biological process to deliver proteins (antigens)
 + gp96 adjuvant to our immune system
l Gp96 “chaperones” newly-created proteins to the cell
 membrane where they are released and embedded
l Activates a cytotoxic T-cell response to the antigen it is
 carrying when cells die through necrosis
 – Enables MHC I antigen cross-presentation to CD8+ T-cells
l Gp96 + protein are only naturally released via necrosis
 – Exposure of gp96 outside the cell activates an immune
 response to the antigen it is carrying
 – Enables MHC I antigen cross-presentation specifically to
 CD8+ T-cells
l Among the most powerful adjuvants and the only
 adjuvant to show exclusive specificity to CD8+ (“killer”)
 T-cells
 – Provides long-term immunity against the infectious agent
Tethered to our cells with a “KDEL” leash
Endoplasmic Reticulum
Cell Membrane
Antigen
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l Genetically modify tumor cells by “severing the
 leash” that binds the gp96 to the endoplasmic
 reticulum of the cell and replacing it with a
 sequence that pumps gp96 out of the cell
l Enables living cancer cells to “pump-out” their own
 surface antigens along with their gp96 chaperone
 – Mimics necrotic cell death
l Activates a powerful pan-antigen cytotoxic T-cell
 immune response
l “Off-the-shelf” therapy designed to enable a fully
 in vivo attack against a wide variety of cancers
Heat Biologics ImPACT technology removes the leash that binds
gp96 to the cell, replacing with a sequence that allows cells to
continually secrete gp96 along with their “chaperoned” antigen
Cell Membrane
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ImPACT Therapy — “Severing the Leash”
 
 
 
Vaccine Injection
Inject living ImPACT cells
into the patient
ImPACT Therapy — Process
Non-functional
Tumor Cell
Killer
T-Cell
Heat Biologics
creates
genetically
modified tumor
cell lines to
continually
secrete their own
mutated antigens
bound to gp96.
2
Scale-up production
of these living tumor
cells as our “drug” to
treat all patients with
a particular cancer.
Irradiate these cells
so they can’t
replicate and vial for
distribution.
3
Inject these living,
genetically-
modified cells into
patients. These
cells continuously
secrete tumor
proteins bound to
gp96.
4
Secreted proteins
activate killer T-
cells to seek-out
and destroy the
targeted cancer.
5
1
Choose cancer of
interest and
identify a cell line
representative of
that cancer.
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ImPACT — Highlights
An “Off-the Shelf” Therapy to Generate a Pan-antigen T-cell Immune Attack
Approach
•   Allogeneic, “off-the-shelf” treatment
     created from a master cell line
•   No tumor cells, blood or anything else
     extracted from the patient
•   Non-invasive
Benefits
•   Unlimited drug supply enables
     immediate treatment
•   Frequent administration with no patient-
     specific processing
•   Less expensive to produce
     and administer than autologous therapies
     with COGS < 5% of autologous approaches
     with fewer logistical hurdles
• Pan-antigen immune attack
 • Unleashes an immune attack against a
 wide variety of known and unknown
 cancer antigens
• Cytotoxic T-cell exclusive immune response
• Antigen + adjuvant in a single complex
 • Antigen + adjuvant presented simultaneously
 • Activates robust and highly specific immune
 response against secreted cancer antigens
• Continuous secretion of gp96-
 antigen/adjuvant complex
 • Generates more robust and sustained antigen
 -specific immune response
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Heat’s HS-110 Therapy
• Cells are genetically modified to secrete gp96
 and most known (and many unknown) lung
 cancer antigens
• Pan-antigen cytotoxic T-cell immune response
Treatment
• Powerful immune activation
• Positive safety profile based on preclinical
 studies and one clinical study
• The drug is administered in a simple,
 once-a-week injection
Survival Curve for Late-Stage 3B/4
NSCLC Patients*
* Massarelli E. Lung Cancer;2003:39 - Meta Analysis
Current Treatment
•   Surgical Resection
•   Radiation Therapy
•   Chemotherapy
         –    3-6 cycles
         –    Each cycle lasts 3-4 weeks
•   Targeted Therapies
Survival Prospects
•   Median survival ~ 4.5 months*
•   1 year survival ~6%*
Lung Cancer and HS-110 (Viagenpumatucel-L)
Background
“Without any chemotherapy, the average person will live about 4½ months.
With chemotherapy most will live longer and some will live a shorter time. More recent chemotherapy trials have
shown that people live about 3 months longer than if they did not get chemotherapy …
… Even with chemotherapy, the chance of being alive at one year is about 30-50%;
the chance of dying within this year is 50-70%.”
— American Society for Clinical Oncology (ASCO) Guidelines
Lung Cancer is the Second Most Common Cancer in
US with No Reliable Treatment Options for Late-Stage
Patients
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HS-110: Successful Completion of Phase 1 Study
l NIH-funded, open-label, single center investigator-sponsored IND
l 18 patients with late-stage NSCLC
l Enrollment alternating in 3 cohorts after first 8 patients
Stage IIIB/IV NSCLC
Disease progressing at time of Enrollment
Failed multiple lines of prior therapy
Cohort 3
¼ Strength Dose Twice Weekly
(10,000,000 Cells)
Cohort 2
½ Strength Dose Weekly
(20,000,000 Cells)
Cohort 1
1 Dose Every 2 Weeks
(40,000,000 Cells)
Safety
Immune Response,
Tumor Response,
Overall Survival,
Progression Free Survival
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Phase 1 NSCLC Trial Design
 
 
 
HS-110 NSCLC Phase 1 Clinical Trial Results
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l Well-tolerated with no overt toxicity
l Single agent clinical activity in late-stage 3b and 4 non-small cell lung cancer
 – 7 of 15 surviving patients exhibited stable disease
 after single course of therapy
l Immune response observed in 73% (11 out of 15)
 of patients who completed their first course of
 therapy
 – Immune response predictive of survival
 (HR: 0.021, 95% CI:0.002-0.204)
 • The immune responders exhibited a median survival of
 16.9 months (95% CI: 7.1-20) while the immune non-
 responders exhibited a median survival of 4.5 months
 – Two late-stage patients survive >3 years
 • One HS-110 patient alive >3 yrs. and another patient
 still alive >4 yrs.
l Median 1 year overall survival rate of patients in the study was 44% (95% CI:
 21.6-65.1) comparing favorably to a 5.5% rate based on historical control*
 
 
 
Immune Response Predictive of Survival
In 11 of the 15 patients (73%) completing the first course of therapy with HS-110, there was a twofold or greater increase in CD8 cells
secreting interferon gamma (CD8-CTL IFN-γ) following vaccination. The responders saw a threefold increase in median overall survival
compared to non-responders in the trial, from 4.5 months to 16.9 months
Non-Responders
Responders
>3x Extension of Median OS
for Responders
6
12
18
24
30
36
0.25
0.50
1.00
0.75
Months From Treatment Start
0
(N=4)
(N=11)
Hazard Ratio: 0.021
95% CI: 0.002 - 0.204
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HS-110 Lung Cancer Phase 2 Clinical Program
1H 2014
üFinalize Phase 2 protocol
üSubmit revised protocol to FDA
üAnnounce Phase 2 protocol
Specifically designed in collaboration with leading KOLs to be
complementary in combination with next generation oncology
treatments
2H 2014
§Commence patient enrollment and dosing
 
 
 
Phase 2 Protocol Designed to
Complement Next Generation Oncology Treatments
l Address unmet need by offering patients access to investigational agents with
 presumably a more favorable safety profile than chemo in a setting where
 there is little approved in 3rd-line and the efficacy of these agents is minimal
l Maximize antigen expression overlap by testing an adenocarcinoma vaccine
 to an adenocarcinoma population
l Mimic future combinations with checkpoint inhibitors by utilizing low-dose
 cyclophosphamide
l Evaluate the effect of concomitant chemotherapy on the immune response to
 HS-110 and of subsequent chemotherapy after HS-110 tumor response
l Evaluate multiple endpoints due to short time to event in this population
 (overall survival, objective response, disease control rate, PFS, immune
 response, 6-mo OS, 12-mo OS)
l Capture pre- and post-treatment biopsy tissue when appropriate in order to
 correlate antigen expression, TILs and T-cell receptor sequences with
 outcomes, potentially leading to proof of concept and precision in patient
 selection
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Phase 2 HS-110/CY Combo NSCLC Design
3rd-line vs. physician’s choice, continue vaccine in combo with 3L chemo after 1st progression
Randomized
HS-110 + low-dose
CY
Vinorelbine OR
erlotinib OR
gemcitabine OR
paclitaxel
Endpoints
Primary: overall survival
Secondary: immune response
in blood,
PFS, DCR, ORR by irRC and
RECIST
6-mo OS, 12-mo OS
 
Pre- and post-treatment biopsy
tissue for exploratory
biomarker analyses
Arm 1; N=82
Arm 2; N=41
3rd-line - Stage
A
4th-line - Stage
B
HS-110 + Vinorelbine
OR erlotinib OR
gemcitabine OR
paclitaxel
First Progression
1
2
3
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Regimen
l Low-dose cyclophosphamide (CY) 50 mg daily for 7 days q2weeks for 12 weeks or until 1st
 progression
l HS-110 107 cells weekly for 12 weeks then q3 weeks until 2nd irPD or 12 months
 whichever comes first
Sample Size
l 123 patients randomized 2:1
l 80% power with alpha = 0.1 to detect a 50% reduction in the risk of death with 59 events
 in the experimental group and 33 events in the control group
 
 
 
Bladder Cancer and HS-410
Background
l Currently-available treatments have high
 failure rate and are poorly tolerated
l Among highest lifetime treatment cost per
 patient of any cancer due to a high recurrence
 rate
l Opportunity to treat patients with minimal
 residual disease
l No new drug for this patient population in
 >25 years
In 2012 Alone, There Were 73,000 New Cases
of Bladder Cancer Reported and 15,000 Deaths
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HS-410: Bladder Cancer Phase 1/2
l Population includes non-muscle invasive disease, treated with surgery
 followed by 3-6 weeks of BCG therapy
Placebo
N=25
HS-410
Optimal dose N=50
Phase 1/2 - 2 Stage Adaptive Design
Proceed with Optimal Dose
HS-410
Cohort 1
Low Dose N=9
1,000,000 cells
HS-410
Cohort 2
High Dose N=9
10,000,000 cells
93 patient, fully-randomized, placebo-controlled trial
Weekly injections for 12 weeks followed by 3 monthly injections
Trial objectives include safety and
immune response
Trial objectives include safety, immune
response and time to recurrence
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Stage 1
N = 18
Dose Finding
Stage 2
N = 75
Proof of Concept
 
 
 
Key Study Timelines and Milestones
Milestone
Target Completion
First patient enrolled and dosed
ü Q1 2014
Cohort 1 enrollment complete
 Q3 2014
Cohort 2 enrollment initiates
 Q4 2014
Cohort 1 safety and antigen profiles
 Q1 2015
Cohort 2 enrollment complete
 Q1 2015
Cohort 2 safety and antigen profiles
 Q1 2015
Phase 2 enrollment initiates
 Q1 2015
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Phase 1/2 Clinical Trial for Bladder Cancer
 
 
 
Business Development Strategy
1. ImPACT Platform Partnerships
 • Strategy to Partner by indication(s)
 • Use platform for new product discovery
 • Product development by partner
2. Clinical Programs (HS-110, HS-410)
 • Partner at/after Phase 2 data
 • Partner with regional or global rights
 • Retain US commercialization rights
 • Explore co-development partnerships with anti-PD1 & anti-PDL1 products
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Companies
Date
Financials
AZ-Immunocore
Jan ‘14
$20M+300M/
program
Novartis-UPenn
Aug ‘12
$20M+MS
Sanofi-CureVac
Nov ‘11
$33M+200M
Selected Immunotherapy Deals
 
 
 
Financial Snapshot
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Ticker
NASDAQ: HTBX
Shares Outstanding
6,452,341
Share Price*
$4.77
Market Capitalization*
~$30M
Cash as of 3/31/14
$19.4M
Enterprise Value
~$10M
Financial strength to execute on our business plan
*as of market close on May 22, 2014
 
 
 
Multiple Near-Term Milestones
Expected to Build Momentum
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Program
1H 2014
2H 2014
HS-110
Lung Cancer
Program
ü Submit revised protocol to FDA
qInitiate Phase 2 enrollment
HS-410
Bladder Cancer
Program
ü Commence patient dosing
 
qComplete Cohort 1 enrollment
qCohort 1 immune response data
qInitiate Cohort 2 enrollment
3rd Product
qGenerate multiple product
 candidates
qAnnounce 3rd product program
 
Corporate
 q Seek development and commercialization partners
 q Continued grant filings and notifications
 q Additional research developments
 q Various clinical publications
 
 
 
Summary
Clinical Stage Platform Technology Generating Promising Human Data
Data to Date Demonstrate:
•   Positive safety profile
•   Powerful, disease-specific immune activation
•   Immune activation corresponds with increased overall survival
Encouraging
Clinical Data
Strong Clinical Pipeline
•   Phase 2 NSCLC clinical trial and Phase 1/2 bladder cancer trial with
    additional IND submissions planned in other cancer indications
•   Multiple near-term enrollment and data readouts
•   Potential for business development licensing activity
Value Creating
Milestones
Transformational
Technology Platform
Unleashes the immune system against a wide range of
cancers
•   Over a decade of published research and recent clinical data
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