Ampligen has demonstrated in pre-clinical and now
human clinical studies a potential to enhance efficacy of PD-1 and/or
PD-L1 checkpoint inhibitors
Ampligen’s
anti-tumor potential is demonstrated with checkpoint blockade therapies
in human clinical studies for the treatment of triple-negative breast
cancer and advanced recurrent ovarian cancer
Based
on a growing body of clinical data, the Company believes in the
potential to expand Ampligen development into treatment of solid tumors
OCALA, Fla., April 21, 2022 (GLOBE NEWSWIRE) -- AIM ImmunoTech Inc. (NYSE: American AIM) (“AIM”
or the “Company”), an immuno-pharma company focused on the research and
development of therapeutics to treat multiple types of cancers, immune
disorders, and viral diseases, including COVID-19, the disease caused by
the SARS-CoV-2 virus, today provided a summary of clinical data that
support the synergistic potential of Ampligen® (rintatolimod) with
checkpoint blockade therapies.
Thomas Equels,
Chief Executive Officer of AIM, commented, “We have amassed a growing
body of encouraging Ampligen data to date through close collaborations
with leading KOLs at preeminent institutions. These data have not only
affirmed but significantly evolved our belief that Ampligen as a single
agent therapy, as well as in combination with the latest powerful cancer
therapies, has the potential to become a breakthrough therapy for some
of the most difficult to treat and deadly cancers. We are going to
continue working tirelessly to advance Ampligen towards approval and
commercialization with the goal of bringing much needed hope to patients
and solutions to treating physicians around the world.”
Ampligen
is the Company’s dsRNA drug currently being developed for globally
important cancers. Ampligen has shown therapeutic synergy with
checkpoint inhibitors, including increasing survival rates and efficacy,
in the treatment of animal tumors when used in combination with
checkpoint blockade therapies. The first detection of Ampligen’s
synergistic potential with checkpoint blockade therapeutics was
witnessed in pre-clinical mouse models of melanoma and pancreatic
cancers. Additionally, the Company now has data from two clinical
studies — in advanced recurrent ovarian cancer and triple negative
breast cancer — that indicate that the drug may have similar anti-tumor
activity in humans.
“Working with AIM, our
Pancreatic Cancer R&D team at the Buffett Cancer Center did
extensive pre-clinical research demonstrating in animal models that
Ampligen had a significant therapeutic benefit in treating pancreatic
cancer. This March, Prof. C.H.J. van Eijck and his team at Erasmus MC published data in the journal Cancers
showing Ampligen alone was associated with extended overall survival in
late-stage pancreatic cancer of 19 months. Just last week, at AACR,
publications of clinical data by UPMC’s Dr. Bob Edwards in advanced recurrent ovarian cancer, and Roswell’s Dr. Pawel Kalinski in both stage 4 triple negative breast cancer and stage 4 colorectal cancer,
strongly supported the advance of Ampligen into human trials for
patients in pancreatic and other cancers where checkpoint drugs are not
effective,” stated Michael (Tony) Hollingsworth, PhD, Associate
Director, Basic Research, University of Nebraska Medical Center.
“Checkpoint
drugs are powerful and important therapies, but only work on ‘hot’
tumors visible to the immune system, not ‘cold’ tumors that are
immune-silent. Ampligen appears, from these data, to turn cold tumors
into hot tumors and create significant therapeutic potential for a
successful second round of Ampligen plus checkpoint therapy for those
who do not respond to checkpoint therapy alone,” added Robert Edwards,
MD, University of Pittsburgh School of Medicine and University of
Pittsburgh Cancer Institute.
“The two ongoing Roswell Park clinical trials we recently presented findings from
represent milestones in our 10-year-long NIH and DoD-funded research
program aiming to convert immuno-resistant ‘cold’ tumors into ‘hot’ ones
that would be more sensitive to immunotherapy. Seeing both studies
successfully meet their predetermined efficacy endpoint — selective
increase of cytotoxic T lymphocyte markers in tumor tissues — Roswell
Park plans to move forward with critical studies assessing therapeutic
efficacy of the combination of a rintatolimod-based chemokine-modulating
regimen with PD-1 inhibitors, cancer vaccines and/or adoptive T cell
therapies in solid tumors. Observations from our preclinical studies
suggest that this multipronged strategy may benefit patients with
multiple solid-tumor lesions, which are difficult to target
individually,” commented Pawel Kalinski, MD, PhD, Jacobs Family Endowed
Chair of Immunology, Chief of the Division of Translational
Immuno-Oncology and Senior Vice President for Team Science at, Roswell
Park Comprehensive Cancer Center.
The
investigator-initiated, Phase 2, single-arm, efficacy/safety trial to
evaluate the effectiveness of combining intensive locoregional
intraperitoneal (IP) chemoimmunotherapy of cisplatin with IP Ampligen
(TLR-3 agonist) and IV infusion of the checkpoint inhibitor
pembrolizumab (KEYTRUDA®) (IVP) for patients with recurrent
platinum-sensitive ovarian cancer is being conducted by the University
of Pittsburgh Medical Center (UPMC). The Phase 2 trial is designed to
enroll up to 45 subjects using Ampligen in combination with
pembrolizumab to test the combinational activity of checkpoint blockade
therapy where Ampligen is administered by injection in the peritoneal
cavity where the tumor is located.
The Company’s
recently announced positive interim results suggesting induction of T
cell activation together with clinical responses may indicate prognostic
evidence of tumor environment reprogramming that we do not see with
chemotherapy alone and which may extend survival. A total of 17 patients
have been enrolled and 13 were evaluable for response in the ongoing
Phase 2 trial. The observed clinical responses were: 2 complete
responses (15.4%), 3 partial responses (23.1%), 3 stable disease
(23.1%), 5 progressions (38.4%) for a clinical benefit rate (CR+PR+SD)
of 61.6%. From 13 patients, 77 IP wash samples were collected at serial
time points. Measurements in IP washes revealed an acute increase in
granzyme B (GZMB), perforin, TNF alpha, CXCL9, CXCL10 and CXCL11 after
treatment (p<0.05). Longitudinal data revealed a progressive increase
in some biomarkers in the locoregional environment; CXCL9, CXCL10,
CXCL11, perforin and TNF alpha were all increased from baseline levels
at cycle 1 to baseline of cycle 6 (p<0.05). CXCL12 was also increased
acutely after treatment (p<0.05).
The
cytokine CXCL12 observed to increase acutely after treatment functions
as a chemotactic for lymphocytes. The cytokines CXCL9-11 active in
antitumor responses in modulation of the tumor microenvironment (TME) to
favor cytotoxic T cells required for anti-tumor cell immune activity
versus regulatory T cells (Tregs), which function to protect non-tumor
“self” tissue. Granzymes are serine proteases released by cytoplasmic granules within cytotoxic T cells and natural killer (NK) cells. They induce programmed cell death (apoptosis) in the target cell, eliminating cells that have become cancerous.
Perforin is a protein, which creates tubules in the cell membrane
allowing cell lysis. Perforin is a key effector molecule for T-cell- and
natural killer-cell-mediated cytolysis.
A
Phase 1 study was conducted at Roswell Park Comprehensive Cancer Center
in patients with metastatic triple-negative breast cancer using
chemokine modulation therapy, including AIM ImmunoTech Inc.’s drug
candidate, Ampligen®, as well as interferon α-2b and pembrolizumab.
In
the study, six evaluable patients (33-75 years) with mTNBC received 6
doses of Ampligen (200 mg i.v.), IFN α-2b (INTRON-A; 20MU/m2 i.v.) and
COX-2 inhibitor (celecoxib; 2 x 200 mg, p.o.) over 2 weeks, with tumor
biopsies obtained before (within 6 days) and after (within 5 days) CKM.
All patients received follow-up pembrolizumab (200 mg, i.v, Q3 weeks).
Uniform increase of immune markers upon treatment was observed: CD8 mRNA
(6.1-fold; p-0.034), GZMB mRNA (3.5-fold; p=0.058), ratios of CD8
/FOXP3 and GZMB/FOXP3 (5.7-fold; p=0.036, and 7.6-fold; p=0.024
respectively), thus successfully meeting the pre-determined primary
endpoint in the study (increase in CD8 in TME). In addition, an increase
in CTL attractants CXCL10 (2.6-fold; p=0.104) and CCL5 (3.3-fold;
p=0.019) was observed. In contrast, Treg marker FOXP3 or Treg
attractants CCL22 or CXCL12 were not enhanced. Three patients had stable
disease lasting 2.4, 2.5 and 3.8 months, as of data cut off September
1, 2021. An additional patient (non-evaluable) had a partial response
(breast tumor autoamputation) with massive tumor necrosis in the
post-CKM biopsy.
Results from this proof-of-concept study
indicated that short-term systemic chemokine modulating regimen (CKM)
followed by pembrolizumab is generally well tolerated and selectively
enhances local cytotoxic T-lymphocytes (CTLs) infiltration in the tumor
microenvironment (TME), providing rationale for concurrent CKM and PD1
blockade in prospective Phase 2 studies.
Based
on the pre-clinical and human clinical data seen to-date, the Company
believes Ampligen has the potential to expand into treatment of solid
tumors.
About AIM ImmunoTech Inc.
AIM
ImmunoTech Inc. is an immuno-pharma company focused on the research and
development of therapeutics to treat multiple types of cancers, immune
disorders, and viral diseases, including COVID-19, the disease caused by
the SARS-CoV-2 virus.
This
press release contains forward-looking statements within the meaning of
the Private Securities Litigation Reform Act of 1995 (the “PSLRA”).
Words such as “may,” “will,” “expect,” “plan,” “anticipate” and similar
expressions (as well as other words or expressions referencing future
events or circumstances) are intended to identify forward-looking
statements. Many of these forward-looking statements involve a number of
risks and uncertainties. Among other things, for those statements, the
Company claims the protection of safe harbor for forward-looking
statements contained in the PSLRA. The Company does not undertake to
update any of these forward-looking statements to reflect events or
circumstances that occur after the date hereof. Many of the studies
discussed above were proof of concept and will require further studies.
Studies and trials are subject to many factors including lack of
regulatory approval(s), lack of study drug, or a change in priorities at
the institutions sponsoring other trials. Significant additional
testing and trials will be required to determine whether Ampligen will
be an effective treatment of cancer or otherwise, and no assurance can
be given that this will be the case.
BioFlorida is the voice of Florida's life sciences industry, representing 8,600 establishments and research organizations in the BioPharma, MedTech, Digital Health and Health Systems that collectively employ nearly 107,000 Floridians. Source: TEConomy/BIO (released 2022)
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