Form: 8-K

Current report filing

January 13, 2014

Corporate Presentation
January 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, 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 Registration Statement on Form S-1, as amended, declared effective by the
Securities and Exchange Commission on July 23, 2013 and our quarterly report on Form 10-Q for the period ended September 30,
2013 (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 clinical data yielding impressive survival supports 2
 programs advancing into late-stage studies in 2014
Ø Clinical development programs with clear path to registration in high-
 potential markets
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 and Scientific Advisory Board
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 Regulatory 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
§ Eckhard R. Podack, M.D., Ph.D.
§ James Allison, Ph.D.
§ Sol J. Barer, Ph.D.
§ John Nemunaitis, M.D.
§ Justin Stebbing, M.D., Ph.D.
§ Daniel D. Von Hoff, M.D.
WORLD RENOWNED
SCIENTIFIC ADVISORY BOARD
Team with Proven Track Record
 
 

 
Diverse Pipeline with Multiple Registration Opportunities
6
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
7
 
 

 
Heat’s ImPACT Therapy
Living Drug Factories
Antigen and adjuvant delivery in a single package
8
 
 

 
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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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
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-410 Lung Cancer Program Next Steps
1H 2014
üFinalize Phase 2 protocol
üSubmit revised protocol to FDA
üAnnounce Phase 2 protocol
üCommence patient enrollment and dosing
Lung cancer Phase 2 program designed in collaboration with KOLs
 
 

 
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 Drug manufacturing and preparation of IND and protocol
 for HS-410 in progress
l No new drugs for this patient population in >25 years
l HS-410 Phase 1/2 trial will include ~93 patients
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 Study opened for enrollment December 2013
l Patient recruitment ongoing
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
 
 

 
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
6,375,426
Share Price*
$7.98
Market Capitalization*
~$50M
Cash as of 9/30/13
$23.6M
Financial strength to execute on our business plan
*as of market close on January 9, 2014
 
 

 
Near-Term Milestones
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Program
1H 2014
2H 2014
HS-110
Lung Cancer
Program
qSubmit revised protocol to FDA
qInitiate Phase 2 enrollment
qPhase 2 patient dosing
qPreliminary data
HS-410
Bladder Cancer
Program
qCommence patient dosing
qComplete Cohort 1 enrollment
 
qCohort 1 immune response data
3rd Product
qGenerate multiple product
 candidates
qAnnounce 3rd product program
 
Corporate
 q Seek development and commercialization partners - Ongoing
 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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