Agenus (NASDAQ: AGEN), an immuno-oncology company with an extensive
pipeline of checkpoint antibodies, adjuvants, and vaccines designed
to activate immune response to cancers and infections, today
announced the presentation of new clinical data for AGEN1181
(Fc-enhanced anti-CTLA-4) as monotherapy and in combination with
balstilimab (anti-PD-1) at the Society for Immunotherapy of Cancer
(SITC) 36th Annual Meeting.
“AGEN1181 as monotherapy and in combination with balstilimab has
shown durable responses in heavily pre-treated, poorly immunogenic
‘cold’ cancers, as well as those who have failed to respond to
prior PD-1 inhibition,” said Steven O’Day, MD, Chief Medical
Officer of Agenus. “This regimen is well tolerated, with no
hypophysitis, pneumonitis, or high-grade hepatitis observed to
date. The clinical performance of AGEN1181 is consistent with its
Fc-enhanced design, safely expanding the benefit of immunotherapy
to a broader patient population.”
Evidence of single agent activityAs of the data
cut-off date of September 17, 2021, one hundred and sixteen
patients received AGEN1181 in a dose escalation study to determine
the optimal monotherapy dose and combination dose with balstilimab.
Of note, this population was heavily pre-treated, with over half of
these patients receiving at least 3 prior lines of therapy and
nearly a third of patients receiving prior anti-PD-1 therapy. There
were four cases of confirmed objective responses to AGEN1181
monotherapy. These include a complete response (CR) in MSS
endometrial cancer, and partial responses (PR) in pancreatic
cancer, as well as PD-1 refractory cervical cancer. These are the
first reported responses to CTLA-4 monotherapy in these disease
settings. The fourth response was in a patient with PD-1 refractory
melanoma. Of note, three of the monotherapy responders expressed
the low affinity FcγRIIIA receptor, which is associated with lack
of response to first-generation CTLA-4 inhibitors1.
Balstilimab combination benefits >60% of
patientsSignificant benefit was also observed with the
combination of AGEN1181 and balstilimab across multiple “cold”
cancers studied, with >60% of evaluable patients receiving at
least 1 mg/kg AGEN1181 experiencing disease control. Among 20
evaluable patients with microsatellite stable colorectal cancer
(MSS-CRC), where PD-1 inhibitors have historically shown limited to
no activity2-5, there were three confirmed PRs and one unconfirmed
PR. In addition, ten cases of stable disease (SD) were observed,
with one patient’s tumor burden reduced by 27%. The disease control
rate (DCR) among these MSS CRC patients was 70%.
Among 9 evaluable ovarian cancer patients receiving at least 1
mg/kg of AGEN1181 in combination with balstilimab, there were three
confirmed PRs and two cases of SD (one of the patients with SD had
a 28% reduction of tumor burden). Compelling clinical activity was
also seen in MSS-endometrial cancer as both patients treated with
combination therapy demonstrated PRs; all three patients with MSS
endometrial cancer treated with AGEN1181 (one with monotherapy, two
in combination with balstilimab) had objective responses.
Additional responders to combination therapy include 1 confirmed PR
in a NSCLC patient who failed prior PD-1 therapy, 2 confirmed PRs
in visceral angiosarcoma, and 1 unconfirmed PR in
leiomyosarcoma.
Responses in this Phase 1 trial have been durable, with half
lasting at least 24 weeks and the majority ongoing.
“AGEN1181 as monotherapy and in combination with balstilimab has
shown promising activity in patients with poorly immunogenic tumors
such as MSS-CRC, endometrial and ovarian cancers; these are tumor
types that do not traditionally respond well to single agent anti
PD-1/PD-L1 therapy,” said Anthony El-Khoueiry, MD, Phase I Program
Director and Associate Professor of Clinical Medicine at Keck
School of Medicine of University of Southern California (USC). Dr.
El-Khoueiry is also an oncologist at the USC Norris Comprehensive
Cancer Center, part of Keck Medicine of USC. “Importantly, multiple
responders expressed the low affinity FcγRIIIA receptor, a feature
that makes them less likely to respond to first-generation CTLA-4
antibodies. Together, this highlights the potential of AGEN1181 to
fulfill unmet medical needs in the current treatment landscape by
overcoming limitations of approved immunotherapies.”
Differentiated safety profile versus first generation
CTLA-4 inhibitorsAGEN1181 was well tolerated with no
hypophysitis, pneumonitis, or high-grade hepatitis. Rates of
gastrointestinal and skin toxicities were comparable to those
observed with first-generation CTLA-4 inhibitors.
Phase 2/3 trials to be initiated in colorectal and
gynecological cancersBased on these data, multi-arm,
randomized phase 2/3 trials investigating AGEN1181 as monotherapy
and in combination with balstilimab in MSS-CRC and gynecological
cancers (ovarian and MSS-endometrial cancer) are being initiated.
The design of these trials may support a potential filing for full
and/or accelerated approval based on the magnitude of benefit
demonstrated in the studies. Combination studies of AGEN1181 with
AGEN2373, a conditionally active CD137 agonist, are expected to
begin later this year in PD-1 refractory melanoma.
Presentation Details:Abstract
Title: AGEN1181, an Fc-enhanced anti-CTLA-4 antibody,
alone and in combination with balstilimab (anti-PD-1) in patients
with advanced solid tumors: Initial phase I results
(NCT03860272)Abstract Number:
479Presenting Author: Dr. Anthony El-Khoueiry
The poster presentation can be accessed in the investor section
of our website at
https://investor.agenusbio.com/events-and-presentations.
In addition, Dr. Steven O’Day, Chief Medical Officer at Agenus
and Dr. Manuel Hidalgo, Chief of the Division of Hematology and
Medical Oncology at Weill Cornell Medicine and
NewYork-Presbyterian/Weill Cornell Medical Center, will participate
in a webcast hosted by Dr. Matt Phipps, biotechnology analyst at
William Blair on Friday, November 12, 2021 at 12:00 p.m. ET.
Registration for the webinar can be done in advance at
https://williamblair.zoom.us/webinar/register/WN_WzxgjO1MRw6dKIWm3nAg-w
A replay will be available after the call for 30 days on the
Events & Presentations page of the Agenus website at
https://investor.agenusbio.com/events-and-presentations.
References:1 F Arce Vargas et al. Cancer Cell. 2018 Apr
9;33(4):649-663.e42 J Brahmer et al. N Engl J Med 2012;
366:2455-24653 S Topalian et al. N Engl J Med 2012; 366:2443-24544
D Le et al. Journal of Clinical Oncology 34, no. 15_suppl (May 20,
2016) 103-1035 C Eng et al. Lancet Oncol 2019; 20: 849–61
Disclosures:Dr. El-Khoueiry has served as a consultant for
Agenus.
About AGEN1181AGEN1181 is a next-generation,
Fc-enhanced, immunoglobulin G1 (IgG1) antibody designed to block
CTLA-4 (cytotoxic T-lymphocyte associated antigen 4) from
interacting with its ligands CD80 and CD86. The Fc region of the
antibody was engineered to enhance potency, improve safety, and
benefit a broader patient population versus first-generation anti
CTLA-4 antibodies. CTLA-4 is a negative regulator of immune
activation that is considered a foundational target within the
immuno-oncology market.
About BalstilimabBalstilimab is a novel, fully
human monoclonal immunoglobulin G4 (IgG4) designed to block PD-1
(programmed cell death protein 1) from interacting with its ligands
PD-L1 and PD-L2. PD-1 is a negative regulator of immune activation
that is considered a foundational target within the immuno-oncology
market.
About Agenus
Agenus is a clinical-stage immuno-oncology company focused on
the discovery and development of therapies that engage the body's
immune system to fight cancer. The Company's vision is to expand
the patient populations benefiting from cancer immunotherapy by
pursuing combination approaches that leverage a broad repertoire of
antibody therapeutics, adoptive cell therapies (through its
affiliate MiNK Therapeutics), adjuvants, and proprietary cancer
vaccine platforms. The Company is equipped with a suite of antibody
discovery platforms and a state-of-the-art GMP manufacturing
facility with the capacity to support clinical programs. Agenus is
headquartered in Lexington, MA. For more information, please visit
www.agenusbio.com and our Twitter handle @agenus_bio. Information
that may be important to investors will be routinely posted on our
website and Twitter.
Forward-Looking StatementsThis press release
contains forward-looking statements that are made pursuant to the
safe harbor provisions of the federal securities laws, including
statements relating to the use of therapeutic candidates AGEN1181,
balstilimab, and AGEN2373, for instance, statements regarding
therapeutic benefit and efficacy, mechanism of action, potency,
durability, and safety profile of the therapeutic candidates, both
alone and in combination with each other and/or other agents, and
the accuracy of top line or interim data; statements regarding
future clinical and regulatory development plans for AGEN1181 alone
and in combination with other agents, including balstilimab and
AGEN2373 ; our ability to obtain regulatory approval for AGEN1181,
alone and in combination with other agents, including balstilimab,
including the timing (including the possibility of accelerated
review) and scope of any such regulatory approval; future
commercial plans, alone and in combination with other agents; and
any other statements containing the words "may," "believes,"
"expects," "anticipates," "hopes," "intends," "plans," "forecasts,"
"estimates," "will" and similar expressions are intended to
identify forward-looking statements. These forward-looking
statements are subject to risks and uncertainties that could cause
actual results to differ materially. These risks and uncertainties
include, among others, the factors described under the Risk Factors
section of our most recent Quarterly Report on Form 10-Q or Annual
Report on Form 10-K filed with the Securities and Exchange
Commission. Agenus cautions investors not to place considerable
reliance on the forward-looking statements contained in this
release. These statements speak only as of the date of this press
release, and Agenus undertakes no obligation to update or revise
the statements, other than to the extent required by law. All
forward-looking statements are expressly qualified in their
entirety by this cautionary statement.
ContactAgenus Inc.Divya
Vasudevan, PhD781-674-4571divya.vasudevan@agenusbio.com
Agenus Media RelationsKimberly HaKKH
Advisors917-291-5744kimberly.ha@kkhadvisors.com
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