In connection with
the announcement of the preliminary results from the Company’s Phase 1a clinical trial, the Company is announcing the following
updated overview of the Company’s business and summary of recent developments.
Overview
We are a biopharmaceutical
company focused on the discovery, development and commercialization of novel therapeutics. Our mission is to bring hope with life-changing
therapies to patients and families that are affected by rare and niche allergic and immunological diseases. Our lead product candidate
is STAR-0215, a potential best-in-class monoclonal antibody inhibitor of plasma kallikrein in clinical development for the treatment of
hereditary angioedema (“HAE”), a rare, debilitating and potentially life-threatening disease. STAR-0215 has the potential
to be the most patient-friendly chronic treatment option for HAE, based on the preclinical and clinical data generated to date and the
existing HAE treatment landscape.
The treatment
options for patients with HAE have improved, however, there is remaining unmet medical need and the global market for HAE therapy is
strong and growing. We estimate that the global HAE therapy market was approximately $2.3 billion in 2021 and that it has the
potential to grow to $4.5 billion by 2027 due to earlier diagnosis of patients, an increase in patients taking preventative
treatments and geographic expansion for currently available therapies. Our vision for STAR-0215 is to develop a best-in-class
monoclonal antibody inhibitor of plasma kallikrein able to provide long-acting, effective attack prevention for HAE with dosing once
every three months or longer. Targeted plasma kallikrein inhibition can prevent HAE attacks by suppressing the pathway that
generates bradykinin and causes excessive swelling. In an in vitro preclinical study, we observed that STAR-0215 is at least
as potent as lanadelumab, a plasma kallikrein inhibitor that has been approved by the U.S. Food and Drug Administration (the
“FDA”), for the treatment of HAE, in inhibiting the generation of bradykinin. In an in vivo preclinical study in
non-human primates, we observed that STAR-0215 has a half-life that is approximately three time longer than lanadelumab. We
submitted an Investigational New Drug application (“IND”) for STAR-0215 in June 2022 and the FDA cleared the IND for
STAR-0215 in July 2022. We initiated a Phase 1a clinical trial for STAR-0215 in August 2022. The Phase 1a randomized, double blind,
placebo controlled single ascending dose clinical trial is evaluating the safety, pharmacokinetics (“PK”) and
pharmacodynamics (“PD”) of STAR-0215 at a single U.S. center. We have enrolled 25 healthy subjects who have received a
single dose of STAR-0215 or placebo in three cohorts of 100mg, 300mg, and 600mg administered subcutaneously, with subjects in each
cohort randomized 3:1 to receive active drug vs. placebo. Subjects in the trial are being followed for safety, PK and PD for a total of up to 224 days.
Recent Developments
On December 15, 2022,
we reported preliminary data from our Phase 1a clinical trial of STAR-0215. The preliminary data were based on a data cut-off date of
December 5, 2022 and include safety data with respect to all enrolled subjects for 84 days following administration and PK and PD data
with respect to the subjects enrolled in the 100mg and 300mg cohorts for 84 days following administration and 56 days following administration
for the subjects enrolled in the 600mg cohort.
Key findings as of the
data cut-off date include:
| · | STAR-0215 was well-tolerated at all dose levels. The most common treatment-related adverse event was mild (Grade 1) self-resolving
injection site reaction, which most commonly was site redness. There were no clinically relevant changes in liver enzymes or coagulation
parameters, serious adverse events or discontinuations. |
| · | Administration of STAR-0215 resulted in rapid and sustained achievement of drug levels consistent with levels associated with clinical
benefit, with the observed concentrations of STAR-0215 being proportional to dose levels. |
| · | PK and PD results in the 300mg and 600mg cohorts were consistent with levels associated with clinical benefit
for up to three months. |
| · | The estimated half-life of STAR-0215 was up to 110 days, which supports dosing once every 3 months or potentially less frequently. |
| · | Modeling of the PK results suggests that an initial 600mg dose of STAR-0215 followed by 300mg doses every three months
thereafter would potentially be capable of maintaining drug concentration levels above the threshold associated with clinical
benefit. |
| · | PD results showed rapid and robust target engagement with plasma kallikrein inhibition through at least three months following a single
dose of STAR-0215. Administration of STAR-0215 resulted in statistically significant reductions in factor XIIa-activated cleaved high
molecular weight kininogen (“cHMKW”) through 84 days in the 300mg cohort and through the latest measurement date in the 600mg
cohort, which was day 56, with levels of inhibition of cHMKW consistent with levels shown to prevent HAE attacks. |
Based on these preliminary
data, we plan to initiate a Phase 1b/2 proof of concept trial called ALPHA-STAR, or Astria Long-Acting Prophylaxis for Hereditary Angiodema:
STAR-0215, in participants with HAE in the first quarter of 2023. This Phase 1b/2 trial will be a global, multi-center, open-label, single
and multiple dose proof-of-concept clinical trial in people with HAE and will evaluate safety, tolerability, HAE attack rate, PK, PD and
quality of life in patients. Each qualifying participant will receive at least one dose of STAR-0215 and may be eligible to roll into
a long-term open label trial. With the ALPHA-STAR clinical trial, we aim to demonstrate durable activity compatible with robust clinical
benefit in people living with HAE and to use the results to inform dose selection for a Phase 3 pivotal trial. We expect to report initial
results from the single and multiple dose cohorts in mid-2024.
The preliminary data from
the Phase 1a trial also suggest that there could be an opportunity to dose STAR-0215 less frequently than every three months. As a result,
we plan to evaluate the potential for 6-month dosing with additional healthy subject cohorts in the Phase 1a trial starting in the first
quarter of 2023 with initial results expected in the fourth quarter of 2023.
In addition, the Company
is supplementing the risk factors previously disclosed in its Annual Report on Form 10-K for the fiscal year ended December 31, 2021 (the
“2021 Form 10-K”) with the following risk factor. This risk factor should be read in conjunction with the risk factors included
in the 2021 Form 10-K.
Interim topline
and preliminary data from our clinical trials that we announce or publish from time to time may change as more patient data become available
and are subject to audit and verification procedures that could result in material changes in the final data.
From time to time,
we may publish interim topline or preliminary data from our clinical trials. Interim data from clinical trials that we may complete
are subject to the risk that one or more of the clinical outcomes may materially change as patient enrollment continues and more
patient data become available. Preliminary or topline results also remain subject to audit and verification procedures that may
result in the final data being materially different from the preliminary data we previously published. As a result, interim and
preliminary data should be viewed with caution until the final data are available. Adverse differences between preliminary or
interim data and final data could significantly harm our reputation and business prospects.
Exhibits
Forward Looking Statements
This Current Report on Form 8-K contains
forward-looking statements within the meaning of applicable securities laws and regulations, including statements with respect to:
expectations regarding the potential significance of the preliminary results from the Phase 1a STAR-0215 trial, the plans to add
additional cohorts to the trial and the anticipated nature and timing of receipt of the data from such additional cohorts;
expectations regarding the timing of initiation, design and timing and nature of the anticipated proof of concept results from
the planned Phase 1b/2 clinical trial of STAR-0215; the longer term development plans for STAR-0215; the potential attributes and
differentiated profile of STAR-0215 as a treatment for HAE, including its potential best-in-class pharmacokinetic profile, potential
dosing frequency, clinical benefit and those suggested by the preliminary results from the STAR-0215 Phase 1a trial, preclinical and
pharmacokinetic modeling data; the potential commercial opportunity for STAR-0215 in HAE; the need for effective treatments for
HAE; the potential for six-month dosing of STAR-0215; and the Company’s goal to meet the unmet needs of patients with rare and
niche allergic and immunological diseases. We use words such as "aims," “anticipate,”
“believe,” “estimate,” “expect,” "goals," “hope,”
“intend,” “may,” "opportunity," “plan,” “predict,” “project,”
“target,” “potential,” “would,” "vision," “can,” “could,”
“should,” “continue,” and other words and terms of similar meaning to help identify forward-looking
statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially
from those indicated by such forward-looking statements as a result of various important factors, including risks and uncertainties
related to: changes in applicable laws or regulations; the possibility that we may be adversely affected by other economic,
business, and/or competitive factors, including the COVID-19 pandemic; risks inherent in pharmaceutical research and development,
such as: adverse results in our drug discovery, preclinical and clinical development activities, the risk that the results of
pre-clinical studies may not be replicated in clinical studies, that the preliminary results from the Phase 1a trial may not be
indicative of the final results, that the results of early stage clinical studies may not be replicated in later stage clinical
studies, the risk that we may not be able to enroll sufficient patients in our clinical trials on a timely basis, and the risk that
any of our clinical trials may not commence, continue or be completed on time, or at all; decisions made by, and feedback received
from, the U.S. Food and Drug Administration and other regulatory authorities on our regulatory and clinical
trial submissions and other feedback from potential clinical trial sites, including investigational review boards at such
sites, and other review bodies with respect to STAR-0215 and any other future development candidates; our ability to manufacture
sufficient quantities of drug substance and drug product for STAR-0215 and any other future product candidates on a cost-effective
and timely basis, and to develop dosages and formulation for STAR-0215 and any other future product candidates that are
patient-friendly and competitive; our ability to develop biomarker and other assays, along with the testing protocols
therefore; our ability to obtain, maintain and enforce intellectual property rights for STAR-0215 and any other future product
candidates; our potential dependence on collaboration partners; competition with respect to STAR-0215 or any of our other future
product candidates; the risk that survey results and market research may not be accurate predictors of the commercial landscape for
HAE and the anticipated position and attributes of STAR-0215 in HAE based on its clinical data to date, pre-clinical profile,
pharmacokinetic modeling and other data; our ability to manage our cash usage and the possibility of unexpected cash expenditures;
our ability to obtain necessary financing to conduct our planned activities and to manage unplanned cash requirements; the risks and
uncertainties related to our ability to recognize the benefits of any additional acquisitions, licenses or similar transactions; and
general economic and market conditions; as well as the risks and uncertainties discussed in the “Risk Factors” section
of our Annual Report on Form 10-K for the period ended December 31, 2021, and in other filings that we may make with the Securities
and Exchange Commission. These forward-looking statements should not be relied upon as representing our view as of any date
subsequent to the date of this Current Report on Form 8-K, and we expressly disclaim any obligation to update any forward-looking
statements, whether as a result of new information, future events or otherwise, except as required by law.