INT230-6 demonstrated a systemic increase in
the median diversity of T-cell repertoire in patients' blood
compared to baseline that was also much larger than a control
saline injection
A single injection of INT230-6 can induce up
to >95% necrosis of a tumor
INT230-6 demonstrated an increase in CD4
T-cells and NK cells within tumors
Gene expression profiling revealed treatment
effect of up-regulation of immune pathways expressed by T-cell
activation, lymphocyte activation and inflammatory
responses
INT230-6 demonstrated a favorable safety
profile and was well tolerated
Patient interest in the new treatment was
high
SHELTON,
Conn., Dec. 8, 2023 /PRNewswire/ -- Intensity
Therapeutics, Inc. (Nasdaq: INTS), a clinical-stage biotechnology
company focused on the discovery and development of proprietary,
novel immune-based intratumoral cancer therapies designed to kill
tumors and increase immune system recognition of cancers, today
announced that safety, tolerability, efficacy and immune activation
data from the company's Phase 2 INVINCIBLE trial of
INT230-6 in patients with early-stage breast cancer without
chemotherapy was presented at a Podium Poster Spotlight discussion
session today during the 2023 San Antonio Breast Cancer Symposium
(SABCS). Information on the presentation is below.
Concurrent Poster Spotlight Session Block #6
PS16
Enhancing Immunotherapy for Triple Negative Breast Cancer: Novel
Therapies and Biomarkers
Moderator: Hope S. Rugo, MD,
FASCO, University of California San
Francisco Helen Diller Family Comprehensive Cancer Center,
San Francisco, California
Title: Intra-tumoral dosing of INT230-6 in early-stage
breast cancer patients induces tumor cell necrosis
and immunomodulatory effects: A phase II randomized
window-of-opportunity study – the INVINCIBLE trial
Presentation #: PS16-03
Date and Time: Friday, December 8, 7:00 – 8:00 a.m. CT
Location: Stars at Night Ballroom 3 & 4
Presenter: Angel Arnaout, M.D., MSc, Ottawa Hospital
Research Institute, Ontario Institute for Cancer Research
Discussant: Sangeetha Reddy,
M.D., M.S.C.I., UT Southwestern Medical Center, Dallas, Texas
Copies of the presentation materials are available on
Intensity's website on the publications, papers and posters
page.
"A large unmet need in the treatment of breast cancer is that
the majority of breast cancers are immune quiescent; resulting in
minimal response to immunotherapies. INT230-6 has the potential to
fill this unmet need for multiple subtypes, including triple
negative breast cancer, through its unique multiple anti-cancer
mechanisms of action that cause tumor cell necrosis, ignition of an
anti-cancer immune-based activation, increasing the diversity of
the T-cell repertoire systemically that can enter into the tumor
and its microenvironment," said Angel Arnaout, M.D.,MSc., Breast
Surgical Oncologist at the Ottawa Hospital, Scientist at the Ottawa
Hospital Research Institute, Professor of Surgery at the
University of Ottawa and Co-Lead of the
Ontario Institute for Cancer Research's Window-of-Opportunity
Network. "The ability for INT230-6 to induce necrosis and noted
immune effects prior to a patient's surgery, while maintaining a
favorable safety profile, would be a major move forward for the
treatment paradigm of breast cancer and potentially many other
cancers."
"I am encouraged by the immune-related data being reported and
the potential of INT230-6 as a presurgical treatment for women
suffering from early-stage breast cancer," said Melanie Spears, Ph.D., Co-Director of Diagnostic
Development and Co-Lead of the Window-of-Opportunity Network at the
Ontario Institute for Cancer Research. "The localized effect of
increased CD4 T-cells and NK cells within injected tumors and
systemically increased T-cell diversity from baseline in these
patients is quite interesting and remarkable for a
locally-delivered therapy."
The INVINCIBLE Trial is a Phase 2, randomized study that
enrolled women with newly diagnosed, operable early-stage
intermediate or high-grade T1-T2 invasive breast cancers 2 to 5
weeks prior to surgery (lumpectomy or mastectomy). Drug dose was
set by the diameter of the tumor. Subjects were randomly allocated
(2:1) prior to resection to 1-3 IT injections of INT230-6 versus
either no treatment (part 1 N=29) or saline sham injection (part 2
N=58). Several markers normally associated with systemic
treatment were evaluated.
Efficacy Data:
The INVINCIBLE Phase 2 trial of
INT230-6 demonstrated a high order of necrosis in presurgical
breast cancer tumors in the period from diagnosis to surgery, with
some patients in the Phase 2 study experiencing greater than 95%
necrosis of the tumor. A functional pathway enrichment analysis was
conducted and confirmed positive changes in T-cell activation,
lymphocyte activation and inflammatory response. Further, INT230-6
treated patients experienced differential gene expression with an
increase in median clonal diversity compared to baseline as well as
significant changes in the immune cell composition, including CD4
T-cell and NK cells.
Safety Data:
Data show that INT230-6 has a favorable
safety profile and is well tolerated. Over 95% of
treatment-emergent adverse events (TEAEs) were low grade 1 or 2
primarily localized pain, fatigue, and nausea.
"We continue to be impressed with the safety and efficacy of
INT230-6. Today's news about the increase in mean systemic T-cell
clonal diversity is truly exciting because it is a signal of the
strength of adaptive immune response systemically. We believe that
the ability to cause large levels of necrosis on a single dose of
our locally-delivered drug with immune effects in a relatively cold
cancer type such as breast cancer prior to surgery shortly after
diagnosis is truly a new weapon in the war on cancer," said
Lewis H. Bender, President and Chief
Executive Officer of Intensity. "In addition to our anticipated
Phase 3 program in metastatic sarcoma using INT230-6 as a
monotherapy, we are underway in our preparations for a Phase 2/3
clinical program to test INT230-6 in combination with standard of
care neoadjuvant therapy. We see the potential opportunity for our
technology and drug products in both the metastatic and presurgical
settings for many types of cancers."
About T-Cell Repertoire
The adaptive immune system is
one of the body's most powerful defenses. By being able to adapt,
the body's immune cells can be trained to attack undesirable cells
or viruses anywhere in the body. T-cells are an important systemic
component of the adaptive immune system that aid in the destruction
of invaders. Immune repertoire refers to all the unique T-cell
receptor (TCR) and B-cell receptor (BCR) genetic rearrangements.
Only lymphocytes that encounter an antigen with the right receptor
to bind to it will be activated and proliferate during an immune
response, forming a clone of cells with identical antigen receptors
for attack. A greater diversity of T-cell repertoire means there is
higher likelihood for a T-cell to bind to the foreign entity (e.g.
cancer cells) and increase the specific T-cell clonal population to
destroy the invader.
About INT230-6
INT230-6, Intensity's lead proprietary
investigational product candidate, is designed for direct
intratumoral injection. INT230-6 was discovered using Intensity's
proprietary DfuseRx℠ technology platform. The drug is composed of
two proven, potent anti-cancer agents, cisplatin and vinblastine,
and a penetration enhancer molecule (SHAO) that helps disperse
potent cytotoxic drugs throughout tumors for diffusion into cancer
cells. These agents remain in the tumor resulting in a favorable
safety profile. In addition to local disease control, direct
killing of the tumor by INT230-6 releases a bolus of neoantigens
specific to the patient's malignancy, leading to engagement of the
immune system and systemic anti-tumor effects. Importantly, these
effects are mediated without immunosuppression that so often occurs
with systemic chemotherapy.
About Intensity Therapeutics' Clinical
Studies
INT230-6 has completed enrollment of over 200
patients in two phase 2 and phase 1 dose escalation clinical trials
(NCT03058289 and NCT04781725) with various advanced solid
tumors; IT-01 in metastatic disease, and IT-02 the INVINCIBLE
study, in presurgical breast cancer. The Company has a clinical
collaboration agreement with Merck Sharpe & Dohme (Merck) to
evaluate the combination of INT230-6, Intensity's lead product
candidate, and KEYTRUDA® (pembrolizumab), Merck's anti-PD-1
(programmed death receptor-1) therapy, in patients with advanced
pancreatic, colon, squamous cell and bile duct malignancies. The
Company also has a clinical collaboration agreement with
Bristol-Myers Squibb to evaluate the combination of INT230-6 with
Bristol-Myers Squibb's anti-CTLA-4 antibody, ipilimumab, in
patients with advanced liver, breast and sarcoma cancers. Intensity
managed the individual combination arms separately with each
respective partner via a joint development committee. The Company
also executed agreements with the Ottawa Hospital Research
Institute (OHRI) and the Ontario Institute of Cancer Research
(OICR) to study INT230-6 in the INVINCIBLE study, a randomized
controlled neoadjuvant phase 2 study in women with early-stage
breast cancer. Near-term, Intensity expects to file an
Investigational New Drug (IND) application for a Phase 3 study of
INT230-6 in soft tissue sarcoma as well as finalizing the study
design and protocol for a Phase 2/3 program in presurgical breast
cancer.
About Intensity Therapeutics
Intensity Therapeutics is
a late-stage biotechnology company that applies novel engineered
chemistry to turn "cold" tumors "hot" by enabling its aqueous
cytotoxic-containing drug product, INT230-6, to mix and saturate
the dense, high-fat pressurized environment of the tumor. As a
result of the saturation, Intensity's clinical trials have
demonstrated the ability of INT230-6 to kill tumors and elicit an
adaptive immune response within days of injection, representing a
truly novel approach to cancer cell death that holds the potential
to shift the treatment paradigm and turn many deadly cancers into
chronic diseases. For more information about the Company, including
publications, papers and posters about its novel approach to cancer
therapeutics, visit www.intensitytherapeutics.com.
Forward-Looking Statements
Certain statements in this
press release may constitute "forward-looking statements" within
the meaning of the United States Private Securities Litigation
Reform Act of 1995, as amended to date. These statements include,
but are not limited to, statements relating to the expected future
plans, development activities, projected milestones, business
activities or results. We have based these forward-looking
statements on our current expectations and projections about future
events, nevertheless, actual results or events could differ
materially from the plans, intentions and expectations disclosed
in, or implied by, the forward-looking statements we make. These
risks and uncertainties, many of which are beyond our control,
include: the risk that the anticipated milestones may be delayed or
not occur or be changed, as well as other risks described in the
section entitled "Risk Factors" in the Company's SEC filings, which
can be obtained on the SEC website at www.sec.gov. Readers are
cautioned not to place undue reliance on the forward-looking
statements, which speak only as of the date on which they are made
and reflect management's current estimates, projections,
expectations and beliefs. The Company does not plan to update any
such forward-looking statements and expressly disclaims any duty to
update the information contained in this press release except as
required by law.
Investor Relations Contact:
Argot Partners
Jonathan Nugent
Intensity@argotpartners.com
Media Contact:
Argot Partners
David Rosen
david.rosen@argotpartners.com
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