AnaptysBio Announces Positive Rosnilimab Healthy Volunteer Phase 1 Top-Line Data
16 November 2021 - 1:00AM
AnaptysBio, Inc. (Nasdaq: ANAB), a clinical-stage biotechnology
company developing first-in-class antibody product candidates
focused on emerging immune control mechanisms applicable to
inflammation and immuno-oncology indications, today announced
positive top-line data from a randomized placebo-controlled healthy
volunteer single and multiple ascending dose Phase 1 trial of
rosnilimab, its investigational wholly-owned anti-PD-1 agonist
therapeutic antibody, previously known as ANB030. Top-line data
demonstrated favorable safety, pharmacokinetics and pharmacodynamic
results that support advancement of rosnilimab into subsequent
patient trials.
“Agonizing the inhibitory function of PD-1 is an exciting new
approach to T cell modulation,” said Dr. W. Michael Gallatin,
leading anti-inflammatory drug development expert and member of
AnaptysBio’s Research and Development Committee. “These data
support rosnilimab’s potential to specifically target the subset of
T cells expressing PD-1 which are believed to be key drivers of
human autoimmune and inflammatory diseases.”
“We are pleased to report promising results for rosnilimab in
this healthy volunteer Phase 1 trial,” said Dr. Paul F. Lizzul,
chief medical officer of AnaptysBio. “We believe rosnilimab’s
mechanism is broadly applicable to T cell driven inflammatory
diseases and look forward to initiating our AZURE
moderate-to-severe alopecia areata trial.”
A total of 144 subjects were enrolled in the randomized,
double-blind, placebo-controlled healthy volunteer Phase 1 trial,
where single ascending dose (SAD) cohorts were administered single
subcutaneous or intravenous doses of rosnilimab ranging between
0.02mg to 600mg or placebo, while multiple ascending dose (MAD)
cohorts received four weekly subcutaneous doses of rosnilimab
ranging between 60mg and 400mg or placebo. Dose escalation was
conducted subsequent to data safety monitoring board review of
safety and tolerability parameters following each single and
multiple ascending dose level.
Rosnilimab was generally well-tolerated and no dose limiting
toxicities were observed. The most frequent adverse event reported
among SAD cohorts was increased circulating C-reactive protein
levels of mild severity in nine (10%) rosnilimab-dosed subjects
occurring sporadically in a dose-independent manner and a severe
occurrence in one (3.3%) placebo-dosed subject. MAD cohorts
reported headache as the most frequent adverse event with mild
occurrences in three (12.5%) rosnilimab-dosed subjects and none in
placebo subjects. Mild injection site reactions were observed in
two subjects (11.1%) administered with multiple subcutaneous
rosnilimab doses. Two serious adverse events were reported in
single dose cohorts, including obstructive pancreatitis in a
placebo-dosed subject and COVID-19 infection in a rosnilimab-dosed
subject leading to discontinuation which was deemed unrelated to
treatment. No serious adverse events were reported in subjects
receiving multiple doses of rosnilimab or placebo.
Pharmacokinetic analyses demonstrated a favorable profile for
rosnilimab with an estimated two-week half-life for subcutaneous
and intravenous routes of administration and approximately 80%
bioavailability. Low-titer anti-drug antibodies were detected at
low single dose levels in 19 (21%) rosnilimab-dosed subjects, but
none were detected in high single dose or multiple dose subjects.
Full PD-1 receptor occupancy was observed rapidly during the first
week following single subcutaneous rosnilimab doses at or above
60mg, and was maintained for at least 30 days at or above 200mg
single subcutaneous doses. These data support monthly subcutaneous
dosing of rosnilimab for future patient trials.
T Cell Population |
Surface Markers |
Average Change From Baseline |
Total T (Tcon and
Treg) cells |
CD3+ |
<5% change |
Conventional T
(Tcon) cells |
CD3+, CD25low |
<5% change |
PD-1 expressing Tcon
cells |
CD3+, CD25low, PD-1+ |
50% reduction |
High PD-1 expressing Tcon cells |
CD3+, CD25low, PD-1high |
90% reduction |
Total regulatory T (Treg) cells |
CD3+, CD4+, CD25bright, CD127- |
<5% change |
Table 1.
Approximate average change in T cell populations relative to
baseline in SAD cohorts achieving full receptor occupancy between
Day 5 and Day 29 following rosnilimab treatment. |
Rosnilimab’s pharmacodynamic activity resulted in rapid and
sustained reduction in the quantity and functional activity of
PD-1+ T cells, which are known to be pathogenic drivers of
inflammatory diseases. Conventional T (Tcon) cells (CD3+, CD25
low) expressing PD-1, which represented approximately 25% of
peripheral T cells at baseline, were reduced by 50%, including in
both CD4+ and CD8+ subsets, in a dose-dependent manner and in
correlation with receptor occupancy (Table 1). This effect was
maximized on high-PD-1 expressing Tcon cells, which represented
approximately 5% of peripheral T cells, with 90% reduction relative
to baseline. Conversely, total T cells (CD3+), total Tcon cells
(CD3+, CD25low) and total regulatory T (Treg) cells (CD3+, CD4+,
CD25 bright, CD127-) were unchanged (<5% change from baseline),
resulting in a favorable shift in the ratio of PD-1+ Tcon cells to
total Treg cells post-treatment. No effect (<5% reduction
from baseline) was observed on any of the aforementioned cell types
in placebo-dosed subjects. In addition, an antigen-specific
functional T cell recall response, measured as ex vivo
interferon-gamma released in response to tetanus toxoid challenge,
was inhibited in a receptor occupancy dependent manner and was
consistent with the observed reduction of PD-1+ Tcon cells, to a
maximum of approximately 90% relative to baseline within 30 days
following single rosnilimab dose, while placebo administration had
no effect. Based upon these data, we believe rosnilimab’s in vivo
mechanism has the potential to treat T-cell driven human
inflammatory diseases.
About RosnilimabRosnilimab is a wholly-owned
PD-1 agonist antibody developed by AnaptysBio using its somatic
hypermutation technology platform. Genetic studies have
demonstrated that PD-1 pathway mutations increase human
susceptibility to multiple autoimmune diseases and insufficient
PD-1 signaling can lead to dysregulated T cell responses.
Rosnilimab’s activity is anticipated to modulate activated T cells
and may be applicable to treatment of T cell-mediated human
inflammatory diseases. Rosnilimab demonstrated in vivo efficacy in
an animal model of inflammation and ex vivo inhibition of primary
immune cells from alopecia areata patients. AnaptysBio anticipates
initiation of a randomized placebo-controlled 45-patient Phase 2
trial of rosnilimab in moderate-to-severe alopecia areata, called
AZURE, during the upcoming few months.
About AnaptysBioAnaptysBio is a clinical-stage
biotechnology company developing first-in-class antibody product
candidates focused on unmet medical needs in inflammation. The
Company’s proprietary anti-inflammatory pipeline includes
imsidolimab, its anti-IL-36R antibody, previously referred to as
ANB019, for the treatment of dermatological inflammatory diseases,
including generalized pustular psoriasis, or GPP,
moderate-to-severe acne and moderate-to-severe hidradenitis
suppurativa; rosnilimab, its anti-PD-1 agonist program, previously
referred to as ANB030, for treatment of moderate-to-severe alopecia
areata; and its BTLA modulator program, ANB032, which is broadly
applicable to human inflammatory diseases associated with lymphoid
and myeloid immune cell dysregulation. AnaptysBio’s antibody
pipeline has been developed using its proprietary somatic
hypermutation, or SHM platform, which uses in vitro SHM for
antibody discovery and is designed to replicate key features of the
human immune system to overcome the limitations of competing
antibody discovery technologies. AnaptysBio has also developed
multiple therapeutic antibodies in an immuno-oncology collaboration
with GSK, including an anti-PD-1 antagonist antibody (JEMPERLI
(dostarlimab-gxly) GSK4057190), an anti-TIM-3 antagonist antibody
(cobolimab, GSK4069889) and an anti-LAG-3 antagonist antibody
(GSK4074386), and an inflammation collaboration with Bristol-Myers
Squibb, including an anti-PD-1 checkpoint agonist antibody
(CC-90006) currently in clinical development.
Forward-Looking StatementsThis press release
contains forward-looking statements within the meaning of the "safe
harbor" provisions of the Private Securities Litigation Reform Act
of 1995, including, but not limited to the timing of initiation of
our Phase 2 clinical trial of rosnilimab in moderate-to-severe
alopecia areata and the potential of rosnilimab to treat T
cell-mediated human inflammatory diseases. Statements including
words such as “plan,” “continue,” “expect,” or “ongoing” and
statements in the future tense are forward-looking statements.
These forward-looking statements involve risks and uncertainties,
as well as assumptions, which, if they do not fully materialize or
prove incorrect, could cause our results to differ materially from
those expressed or implied by such forward-looking statements.
Forward-looking statements are subject to risks and uncertainties
that may cause the company’s actual activities or results to differ
significantly from those expressed in any forward-looking
statement, including risks and uncertainties related to the
company’s ability to advance its product candidates, obtain
regulatory approval of and ultimately commercialize its product
candidates, the timing and results of preclinical and clinical
trials, the company’s ability to fund development activities and
achieve development goals, the company’s ability to protect
intellectual property and other risks and uncertainties described
under the heading “Risk Factors” in documents the company files
from time to time with the Securities and Exchange Commission.
These forward-looking statements speak only as of the date of this
press release, and the company undertakes no obligation to revise
or update any forward-looking statements to reflect events or
circumstances after the date hereof.
Contact:Dennis MulroyAnaptysBio, Inc.
858-732-0201dmulroy@anaptysbio.com
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