MacroGenics Provides Update on Corporate Progress, First Quarter 2024 Financial Results and Interim TAMARACK Phase 2 Study Data
2024年5月10日 - 5:01AM
MacroGenics, Inc. (NASDAQ: MGNX), a biopharmaceutical company
focused on discovering, developing, manufacturing and
commercializing innovative antibody-based therapeutics for the
treatment of cancer, today provided an update on its recent
corporate progress and reported financial results for the quarter
ended March 31, 2024.
“We are very encouraged by the interim updated safety and
preliminary efficacy data from the TAMARACK study of vobra duo in
metastatic castration-resistant prostate cancer," said Scott
Koenig, M.D., Ph.D., President and CEO of MacroGenics. “We believe
this interim data set helps validate our previously stated
hypothesis that improved tolerability coupled with compelling
biological activity could be achieved through dose reductions and a
longer dosing interval. We believe vobra duo’s biological activity
shown to date aligns well with the parameters we outlined at the
outset of the study. Based on our evaluation of the interim data to
date, we have initiated planning activities for a potential Phase 3
study that could commence next year. We anticipate sharing final
safety, efficacy and durability data, including radiographic
progression-free survival data, which is the primary endpoint of
the study, in the second half of 2024. Furthermore, having
preliminarily identified suitable vobra duo doses in mCRPC in the
TAMARACK study, we have greater confidence in the molecule’s
potential to help patients with a broad range of B7-H3-expressing
cancers.”
“The interim safety and anti-tumor activity observed to date in
the TAMARACK study look very promising for patients with metastatic
castration-resistant prostate cancer,” said Johann DeBono, Regius
Professor of Cancer Research and Professor in Experimental Cancer
Medicine at The Institute of Cancer Research, London and The Royal
Marsden NHS Foundation Trust. “With the limited treatment options
currently available to these patients, this novel ADC molecule
could potentially become the first therapy targeting B7-H3 in
patients with prostate cancer and would represent an important new
treatment for this population.”
Updates on Proprietary Investigational
Programs
Recent progress and anticipated events related to MacroGenics’
investigational product candidates are highlighted below.
B7-H3-Directed Therapies |
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Vobramitamab duocarmazine (vobra duo) is an
antibody-drug conjugate (ADC) that targets B7-H3, an antigen with
broad expression across multiple solid tumors and a member of the
B7 family of molecules involved in immune regulation. |
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MacroGenics completed enrollment of the TAMARACK Phase 2 study of
vobra duo in November 2023. TAMARACK is being conducted in patients
with metastatic castration-resistant prostate cancer (mCRPC) who
were previously treated with one prior androgen receptor
axis-targeted therapy (ARAT). Participants may have received up to
one prior taxane-containing regimen, but no other chemotherapy
agents. The TAMARACK study is designed to evaluate vobra duo at two
different doses: 2.0 mg/kg or 2.7 mg/kg every four weeks
(q4W). |
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A
new presentation of TAMARACK interim data, consisting of updated
safety and preliminary efficacy data, all based on a data cut-off
date of April 12, 2024, is available under "Events &
Presentations" in the Investor Relations section of MacroGenics’
website or directly via this link. Below is a high-level summary of
this interim data, which is subject to further updates: |
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Vobra Duo2.0 mg/kg q4W |
Vobra Duo2.7 mg/kg q4W |
Patients Enrolled |
n=91 |
n=90 |
PSA Reduction Summary: |
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PSA Evaluable Patients |
n=82 |
n=71 |
Any PSA Reduction ≥50% |
41 (50.0%) |
36 (50.7%) |
Confirmed PSA Reduction ≥50% |
36 (43.9%) |
26 (36.6%) |
Tumor Response Summary: |
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RECIST Evaluable Patients with Measurable Disease at Baseline |
n=45 |
n=32 |
Disease Control Rate (CR+PR+SD) |
41 (91.1%) |
28 (87.5%) |
Overall Response Rate (CR+PR, confirmed only) |
8 (17.8%) |
8 (25.0%) |
Overall Response Rate (CR+PR, including unconfirmed) |
11 (24.4%) |
14 (43.8%) |
Safety Summary: |
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Safety Population |
n=90 |
n=86 |
Treatment-Emergent Adverse Events All Grade |
89 (98.9%) |
86 (100.0%) |
Treatment- Emergent Adverse Events Grade ≥3 |
49 (54.4%) |
44 (51.2%) |
TEAE Leading to Study Drug Discontinuation |
10 (11.1%) |
13 (15.1%) |
TEAE Leading to Study Drug Dose Reduction |
39 (43.3%) |
44 (51.2%) |
TEAE Leading to Study Drug Dose Interruption |
38 (42.2%) |
48 (55.8%) |
Five Most Common TEAE All Grade |
Asthenia (46.7%)Nausea (35.6%)Oedema peripheral (32.2%) Decreased
appetite (28.9%) Fatigue (25.6%) |
Asthenia (58.1%)Decreased appetite (37.2%) Oedema peripheral
(36.0%) Nausea (30.2%)Pleural effusion (29.1%) |
Pleural Effusions |
Grade 1=8.9%Grade 2=8.9%No Grade ≥ 3 event |
Grade 1=14.0%Grade 2=14.0%Grade 3=1.2% |
Palmar-plantar Erythrodysaesthesia Syndrome |
Grade 1=11.1%Grade 2=4.4%No Grade ≥ 3 event |
Grade 1=12.8%Grade 2=9.3%Grade 3=1.2% |
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The median number of cycles of vobra duo administered was five
(range of 1-10). |
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A
total of five events with fatal outcome occurred as follows: one
Grade 5 event in the 2.0 mg/kg dosing cohort: acute myocardial
infarction (considered unrelated to study drug by the
investigator); three Grade 5 events in the 2.7 mg/kg dosing cohort:
one cardiac arrest (considered unrelated to study drug by the
investigator) and two events of pneumonitis. In addition, a patient
in the 2.7 mg/kg dosing cohort had a Grade 3 pleural effusion that
is recorded as having a fatal outcome. The latter three deaths are
being investigated, as follow-up is incomplete on this ongoing
trial. |
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Additional data is provided in the presentation on the Company’s
website and as filed with the Securities and Exchange
Commission. |
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Based on a current evaluation of this interim data, the Company is
undertaking the initial steps necessary to prepare for the
potential initiation of a Phase 3 study in mCRPC in 2025. The final
decision to pursue such a Phase 3 study will be based on an
analysis of the final data set, including rPFS, when
available. |
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The Company intends to share final safety, efficacy, and durability
data, including the primary endpoint of radiographic
progression-free survival, from the TAMARACK trial in the second
half of 2024. |
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MacroGenics plans to expand the TAMARACK study of vobra duo by
enrolling patients with non-small cell lung cancer (NSCLC), small
cell lung cancer (SCLC), melanoma, squamous cell carcinoma of the
head and neck (SCCHN) and anal cancer. The Company expects to
initiate dosing in these additional cohorts in mid-2024. |
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MacroGenics continues to enroll a Phase 1/2 dose escalation study
of vobra duo in combination with lorigerlimab in patients with
various advanced solid tumors. The Company anticipates commencing a
dose expansion study of this combination in mCRPC and at least one
additional indication in 2024. |
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MGC026 is a clinical B7-H3-targeting ADC that is
site-specifically conjugated to exatecan, a topoisomerase I
inhibitor payload developed by Synaffix (a Lonza company). With
distinct mechanisms of action, vobra duo and MGC026 may address
different cancers, tumor stages, or be used in combination with
alternate agents — or potentially with one another — to enhance
their clinical utility. A Phase 1 dose escalation study of MGC026
in patients with advanced solid tumors is ongoing.MGC026
preclinical data was presented recently at the American Association
for Cancer Research (AACR) Annual Meeting. In preclinical studies,
MGC026 was shown to have greater potency than B7-H3-directed
antibodies conjugated to deruxtecan, or DXd, a topoisomerase-based
payload utilized in other ADCs. In addition, the MGC026 payload has
been shown to be less susceptible to multi-drug resistance (MDR)
mechanisms than DXd and SN-38. |
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Enoblituzumab is an Fc-optimized monoclonal
antibody that targets B7-H3. The HEAT study, an
investigator-sponsored, randomized Phase 2 clinical trial being
conducted by MacroGenics’ academic collaborators, is ongoing. This
study is being conducted to evaluate the activity of neoadjuvant
enoblituzumab given prior to radical prostatectomy in up to 219 men
with high-risk localized prostate cancer. |
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Lorigerlimab |
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Lorigerlimab is a bispecific, tetravalent PD-1 ×
CTLA-4 DART® molecule. In addition to the ongoing study of
lorigerlimab in combination with vobra duo mentioned above,
MacroGenics is enrolling LORIKEET, a randomized Phase 2 study of
lorigerlimab in combination with docetaxel vs. docetaxel alone in
second-line, chemotherapy-naïve mCRPC patients. A total of 150
patients are planned to be treated in the 2:1 randomized study. The
current trial design includes a primary study endpoint of
radiographic progression-free survival (rPFS). The Company
anticipates completing enrollment of the study in 2024 and
providing a clinical update in the first half of 2025. |
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Emerging ADC Pipeline |
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MGC028 is a preclinical ADC incorporating an
ADAM9-targeting antibody and represents the second MacroGenics ADC
molecule that incorporates Synaffix’s novel site-specific linker
and topoisomerase I inhibitor-based cytotoxic payload. ADAM9 (a
disintegrin and metalloprotease domain 9) is a member of the ADAM
family of multifunctional type 1 transmembrane proteins that play a
role in tumorigenesis and cancer progression and is overexpressed
in multiple cancers, making it an attractive target for cancer
treatment. The Company currently anticipates submitting an
investigational new drug (IND) application for MGC028 by the end of
2024.MGC028 preclinical data was presented recently at the AACR
Annual Meeting. In preclinical studies, MGC028 demonstrated
specific antitumor activity in in vivo models representing gastric,
lung, pancreatic, colorectal cancer, SCCHN and cholangiocarcinoma.
In addition, in a non-human primate study, MGC028 was well
tolerated at high dose levels, with mild, reversible side effects
and no ocular toxicity, which is often a concern with
tubulin-inhibitor-based ADCs. These promising preclinical results
support the continued investigation of MGC028 as a therapeutic
option for treating ADAM9-expressing solid cancers. |
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Partnered Program |
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MGD024 is a next-generation, humanized CD123 × CD3
DART molecule designed to minimize cytokine-release syndrome, while
maintaining anti-tumor cytolytic activity, and permitting
intermittent dosing. MacroGenics continues to enroll patients in a
Phase 1 dose-escalation study of MGD024 in patients with
CD123-positive neoplasms, including acute myeloid leukemia and
myelodysplastic syndromes. Under an October 2022 exclusive option
and collaboration agreement, Gilead Sciences, Inc. has the option
to license MGD024 at predefined decision points during the Phase 1
study. |
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First Quarter 2024 Financial
Results |
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Cash Position: Cash, cash equivalents and
marketable securities balance as of March 31, 2024, was $184.2
million, compared to $229.8 million as of December 31,
2023. |
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Revenue: Total revenue was $9.1 million for the
quarter ended March 31, 2024, compared to total revenue of
$24.5 million for the quarter ended March 31, 2023. The
decrease was primarily due to a decrease in revenue from
collaborative and other agreements, including a $15.0 million
milestone received from Incyte in the quarter ended March 31,
2023. |
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R&D Expenses: Research and development
expenses were $46.0 million for the quarter ended March 31,
2024, compared to $45.9 million for the quarter ended
March 31, 2023. |
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SG&A Expenses: Selling, general and
administrative expenses were $14.7 million for the quarter ended
March 31, 2024, compared to $13.5 million for the quarter
ended March 31, 2023. The increase was primarily related to
increased stock-based compensation expense and other professional
fees. |
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Net Loss: Net loss was $52.2 million for
the quarter ended March 31, 2024, compared to net loss of
$38.0 million for the quarter ended March 31, 2023. |
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Shares Outstanding: Shares of common stock
outstanding as of March 31, 2024 were 62,560,502. |
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Cash Runway Guidance: MacroGenics anticipates that
its cash, cash equivalents and marketable securities balance of
$184.2 million as of March 31, 2024, in addition to projected
and anticipated future payments from partners and product revenues
should extend its cash runway into 2026. The Company’s expected
funding requirements reflect anticipated expenditures related to
the Phase 2 TAMARACK clinical trial, the Phase 2 LORIKEET study as
well as MacroGenics’ other ongoing clinical and preclinical
studies. |
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Conference Call Information
To participate via telephone, please register in advance at this
link. Upon registration, all telephone participants will receive a
confirmation email detailing how to join the conference call,
including the dial-in number along with a unique passcode and
registrant ID that can be used to access the call.
The listen-only webcast of the conference call can be accessed
under "Events & Presentations" in the Investor Relations
section of MacroGenics’ website at
http://ir.macrogenics.com/events.cfm. A recorded replay of the
webcast will be available shortly after the conclusion of the call
and archived on MacroGenics’ website for 30 days following the
call.
MACROGENICS, INC. |
SELECTED CONSOLIDATED BALANCE SHEET DATA |
(Amounts in thousands) |
|
|
March 31, 2024 |
|
December 31, 2023 |
|
(unaudited) |
|
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Cash, cash equivalents and marketable securities |
$ |
184,237 |
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$ |
229,805 |
Total assets |
|
248,285 |
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|
298,418 |
Deferred revenue |
|
79,019 |
|
|
80,894 |
Total stockholders' equity |
|
106,154 |
|
|
152,613 |
MACROGENICS, INC. |
CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE
LOSS |
(Unaudited) |
(Amounts in thousands, except share and per share
data) |
|
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Three Months Ended March 31, |
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2024 |
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2023 |
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Revenues: |
|
|
|
Collaborative and other agreements |
$ |
1,449 |
|
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$ |
16,686 |
|
Product sales, net |
|
4,861 |
|
|
|
3,490 |
|
Contract manufacturing |
|
2,276 |
|
|
|
3,615 |
|
Royalty revenue |
|
160 |
|
|
|
422 |
|
Government agreements |
|
358 |
|
|
|
283 |
|
Total revenues |
|
9,104 |
|
|
|
24,496 |
|
Costs and expenses: |
|
|
|
Cost of product sales |
|
270 |
|
|
|
113 |
|
Cost of manufacturing services |
|
1,846 |
|
|
|
3,410 |
|
Research and development |
|
46,029 |
|
|
|
45,872 |
|
Selling, general and administrative |
|
14,709 |
|
|
|
13,527 |
|
Total costs and expenses |
|
62,854 |
|
|
|
62,922 |
|
Loss from operations |
|
(53,750 |
) |
|
|
(38,426 |
) |
Interest and other income |
|
2,693 |
|
|
|
1,073 |
|
Interest and other expense |
|
(1,133 |
) |
|
|
(656 |
) |
Net loss |
|
(52,190 |
) |
|
|
(38,009 |
) |
Other comprehensive income
(loss): |
|
|
|
Unrealized gain (loss) on investments |
|
(29 |
) |
|
|
13 |
|
Comprehensive loss |
$ |
(52,219 |
) |
|
$ |
(37,996 |
) |
|
|
|
|
Basic and diluted net loss per
common share |
$ |
(0.84 |
) |
|
$ |
(0.61 |
) |
Basic and diluted weighted
average common shares outstanding |
|
62,290,538 |
|
|
|
61,809,817 |
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About MacroGenics, Inc.
MacroGenics (the Company) is a biopharmaceutical company focused
on discovering, developing, manufacturing and commercializing
innovative monoclonal antibody-based therapeutics for the treatment
of cancer. The Company generates its pipeline of product candidates
primarily from its proprietary suite of next-generation
antibody-based technology platforms, which have applicability
across broad therapeutic domains. The combination of MacroGenics'
technology platforms and protein engineering expertise has allowed
the Company to generate promising product candidates and enter into
several strategic collaborations with global pharmaceutical and
biotechnology companies. For more information, please see the
Company's website at www.macrogenics.com. MacroGenics, the
MacroGenics logo, MARGENZA and DART are trademarks or registered
trademarks of MacroGenics, Inc.
Cautionary Note on Forward-Looking
Statements
Any statements in this press release about future expectations,
plans and prospects for MacroGenics (“Company”), including
statements about the Company’s strategy, future operations,
clinical development of the Company’s therapeutic candidates,
including initiation and enrollment in clinical trials, expected
timing of results from clinical trials, discussions with regulatory
agencies, commercial prospects of or product revenues from MARGENZA
and the Company’s product candidates, if approved, manufacturing
services revenue, milestone or opt-in payments from the Company’s
collaborators, the Company’s anticipated milestones and future
expectations and plans and prospects for the Company, as well as
future global net sales of TZIELD and the Company’s ability to
achieve the milestone payments set forth under the terms of the
agreement with DRI (or its successors or assigns with respect to
such agreement), and other statements containing the words “subject
to”, "believe", “anticipate”, “plan”, “expect”, “intend”,
“estimate”, “potential,” “project”, “may”, “will”, “should”,
“would”, “could”, “can”, the negatives thereof, variations thereon
and similar expressions, or by discussions of strategy constitute
forward-looking statements within the meaning of Section 27A of the
Securities Act of 1933 and Section 21E of the Securities Exchange
Act of 1934. Actual results may differ materially from those
indicated by such forward-looking statements as a result of various
important factors, including: risks that TZIELD, vobramitamab
duocarmazine, lorigerlimab, ZYNYZ, MARGENZA or any other product
candidate’s revenue, expenses and costs may not be as expected,
risks relating to TZIELD, vobramitamab duocarmazine, lorigerlimab,
ZYNYZ, MARGENZA or any other product candidate’s market acceptance,
competition, reimbursement and regulatory actions; future data
updates, especially with respect to vobramitamab duocarmazine; our
ability to provide manufacturing services to our customers; the
uncertainties inherent in the initiation and enrollment of future
clinical trials; the availability of financing to fund the internal
development of our product candidates; expectations of expanding
ongoing clinical trials; availability and timing of data from
ongoing clinical trials; expectations for the timing and steps
required in the regulatory review process; expectations for
regulatory approvals; expectations of future milestone payments;
the impact of competitive products; our ability to enter into
agreements with strategic partners and other matters that could
affect the availability or commercial potential of the Company's
product candidates; business, economic or political disruptions due
to catastrophes or other events, including natural disasters,
terrorist attacks, civil unrest and actual or threatened armed
conflict, or public health crises such as the novel coronavirus
(referred to as COVID-19 pandemic); and other risks described in
the Company's filings with the Securities and Exchange Commission.
In addition, the forward-looking statements included in this press
release represent the Company's views only as of the date hereof.
The Company anticipates that subsequent events and developments
will cause the Company's views to change. However, while the
Company may elect to update these forward-looking statements at
some point in the future, the Company specifically disclaims any
obligation to do so, except as may be required by law. These
forward-looking statements should not be relied upon as
representing the Company's views as of any date subsequent to the
date hereof.
CONTACTS: Jim Karrels, Senior Vice President, CFO 1-301-251-5172
info@macrogenics.com
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