- Plan to start Phase 2/3 prostate cancer study with MGC018 by year-end
- Initiated Phase 1 study of MGC018 in combination with lorigerlimab in advanced solid tumors
- Targeting mid-2022 start of Phase 1 study of MGD024 in hematologic malignancies
- Conference call scheduled for today at 4:30 p.m. ET.
“We are very pleased by the progress made during the first quarter. Our recent end of Phase 1 meeting with the
Updates on Proprietary Investigational Programs
- MGC018 is an ADC that targets B7-H3.
- Following a constructive FDA meeting in
March 2022, MacroGenicsfinalized the Phase 2/3 study design of MGC018 in patients with metastatic castration-resistant prostate cancer (mCRPC). The Phase 2/3 study is designed to enroll patients with mCRPC who have had prior exposure to a taxane and at least one androgen receptor axis-targeted, or ARAT, agent (including abiraterone, enzalutamide or apalutimide), and a PARP (poly adenosine diphosphate-ribose polymerase) inhibitor, if appropriate. During the Phase 2 portion of the study, approximately 150 patients are expected to be randomized 1:1:1 to receive either 2.0 mg/kg or 2.7 mg/kg of MGC018 every four weeks in the experimental groups or physician’s choice of an ARAT agent not previously received in the control group. These lower doses compare to the starting dose of 3.0 mg/kg every three weeks (and any subsequent reductions) evaluated in the Phase 1 dose expansion study and are based on modelling and simulation of patient pharmacokinetic and safety data generated across dose expansion cohorts to date. The Company anticipates that the lower doses will decrease both the frequency and severity of adverse events and potentially improve efficacy by allowing patients to stay on therapy longer.
The Company expects analysis of the data to be performed upon completion of the Phase 2 portion of the study. In the Phase 3 portion,
MacroGenicsplans to randomize additional patients 1:1 to receive either MGC018 at the recommended dose or an ARAT agent for the control group. The inclusion of the Phase 2 interim analysis to evaluate the two MGC018 dose levels will allow the Company to further assess safety, tolerability and futility before proceeding to the Phase 3 portion of the study. The primary endpoint of the study will be radiographic progression-free survival (rPFS) and key secondary endpoints include objective response rate (ORR) and overall survival (OS). The Company expects to begin enrollment by year-end 2022.
- MacroGenics’ Phase 1/2 expansion study of MGC018 is fully enrolled for patients with mCRPC (n=40) and smaller cohorts of patients (n=approximately 20 each) with non-small cell lung cancer (NSCLC), melanoma and triple negative breast cancer (TNBC), while the Company continues to recruit patients for the squamous cell carcinoma of the head and neck (SCCHN) cohort. The Company is encouraged by initial clinical activity observed in patients with melanoma and plans to recruit 20 additional melanoma patients in its ongoing dose expansion study, evaluating a dose of 2.7 mg/kg administered every four weeks. As for the other tumor types enrolled in the expansion study, the Company is evaluating possible next steps for enrolling additional patients with NSCLC.
MacroGenicsdoes not plan to proceed with advancing the study in patients with TNBC at this time. The Company intends to provide an update on clinical data from patients in the Phase 1/2 dose expansion study in the second half of 2022. MacroGenicsrecently dosed the first patient in a Phase 1 dose escalation study of MGC018 in combination with lorigerlimab in patients with various advanced solid tumors.
- Finally, in April,
MacroGenicspresented a poster titled “Targeting B7-H3 in Prostate Cancer: Preclinical Proof-of-Concept with MGC018, an Investigational Anti-B7-H3 Antibody-Drug Conjugate,” at the American Association for Cancer Research(AACR) Annual meeting. MGC018 demonstrated anti-tumor effects toward prostate cancer cell lines and enhanced activity in some lines when combined with PARP or androgen-receptor inhibitors.
- Following a constructive FDA meeting in
- Enoblituzumab is an Fc‐engineered, monoclonal antibody that targets B7‐H3.
MacroGenicscontinues to recruit patients into its Phase 2 study of enoblituzumab in front-line patients with SCCHN, in which PD-L1 positive patients receive combination therapy with retifanlimab (anti-PD-1 antibody) and PD-L1 negative patients receive combination therapy with tebotelimab (PD-1 x LAG-3 DART molecule). The Company expects to complete enrollment of the PD-L1 positive patient cohort during the first half of this year and provide an update on this cohort during the second half of the year.
- Updated study results from an earlier Phase 1 study of the combination of enoblituzumab and pembrolizumab in advanced B7-H3-expressing solid tumors was published in the
Journal for ImmunoTherapy of Cancerin April (data cut-off: March 14, 2019). This combination was well tolerated and demonstrated objective responses in 6 of 18 patients (33.3%) with SCCHN who were checkpoint-naïve and had previously progressed after receiving first-line platinum-based chemotherapy. The updated published data showed a median OS of 17.4 months (95% CI: 9.2 to NR) in patients with SCCHN. These encouraging findings helped guide our current development strategy for enoblituzumab.
DART Molecules for Immune Checkpoint Blockade:
- Lorigerlimab is a bispecific, tetravalent DART molecule targeting PD-1 and CTLA-4. During the first quarter of 2022, the Company initiated a combination study of MGC018 with lorigerlimab in patients with various solid tumors.
MacroGenicsis also conducting a Phase 1/2 dose expansion study with lorigerlimab as monotherapy in cohorts of patients with microsatellite stable colorectal cancer (MSS CRC), mCRPC, melanoma and checkpoint-naïve NSCLC. MacroGenicsanticipates sharing data from this ongoing study in the second half of 2022.
Bispecific CD123 × CD3 DART molecule:
- 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 through a longer half-life. In April, MacroGenics’ IND application for MGD024 was cleared by the FDA for evaluation in patients with hematologic malignancies. The Company expects to begin enrollment in a Phase 1 study of MGD024 in patients with CD123-positive neoplasms, including acute myeloid leukemia (AML) in mid-2022.
Other Program Updates:
- Teplizumab is an investigational, anti-CD3 monoclonal antibody acquired from
MacroGenicsby Provention Bio, Inc. under an asset purchase agreement in 2018 for which MacroGenicsis entitled to receive future milestone payments and royalties on net sales. Provention is developing teplizumab for the treatment of type 1 diabetes (T1D). On March 21, 2022, Provention announced that the FDA had accepted the Biologics License Application (BLA) for teplizumab for the delay of clinical T1D in at-risk individuals. The FDA assigned a Prescription Drug User Fee Act (PDUFA) target action date of August 17, 2022.
First Quarter 2022 Financial Results
- Cash Position: Cash, cash equivalents and marketable securities as of
March 31, 2022, were $184.0 million, compared to $243.6 millionas of December 31, 2021.
- Revenue: Total revenue, consisting primarily of revenue from collaborative agreements, was
$11.1 millionfor the quarter ended March 31, 2022, compared to total revenue of $16.9 millionfor the quarter ended March 31, 2021. Revenue for the quarter ended March 31, 2022included $3.6 millionnet sales of MARGENZA. The Company continues to have modest expectations for MARGENZA sales.
- R&D Expenses: Research and development expenses were
$61.4 millionfor the quarter ended March 31, 2022, compared to $53.1 millionfor the quarter ended March 31, 2021. The increase was primarily related to development, manufacturing and clinical trial costs related to MGC018, development of discovery projects and preclinical molecules, and increased clinical expenses related to lorigerlimab. These increases were partially offset by decreased development, manufacturing and clinical trial costs related to flotetuzumab (which development has been discontinued), decreased margetuximab manufacturing costs related to the Zai Lab agreement, and decreased retifanlimab manufacturing costs for Incyte.
- SG&A Expenses: Selling, general and administrative expenses were
$16.3 millionfor the quarter ended March 31, 2022, compared to $15.0 millionfor the quarter ended March 31, 2021. The increase was primarily related to MARGENZA selling costs, as well as stock-based compensation and consulting expenses.
- Net Loss: Net loss was
$66.4 millionfor the quarter ended March 31, 2022, compared to net loss of $51.3 millionfor the quarter ended March 31, 2021.
- Shares Outstanding: Shares outstanding as of
March 31, 2022were 61,333,074.
- Cash Runway Guidance:
MacroGenicsanticipates that its cash, cash equivalents and marketable securities as of March 31, 2022, plus anticipated and potential collaboration payments, and product revenues should enable it to fund its operations through 2023. The Company’s expected funding requirements do not reflect anticipated expenditures related to the full Phase 2/3 development of MGC018 in mCRPC anticipated to begin by year-end 2022, or further expansion of other studies currently ongoing. However, the Company believes that it can reasonably obtain funding for the planned Phase 2 portion of the MGC018 study through a combination of existing financial resources, a variety of external funding or potential revenue sources, and project prioritization.
Conference Call Information
The listen-only webcast of the conference call can be accessed under "Events & Presentations" in the Investor Relations section of the Company's website at http://ir.macrogenics.com/events.cfm. A replay of the webcast will be available shortly after the conclusion of the call and archived on the Company's website for 30 days following the call.
SELECTED CONSOLIDATED BALANCE SHEET DATA
(Amounts in thousands)
|Cash, cash equivalents and marketable securities||$||183,986||$||243,616|
|Total stockholders' equity||178,214||239,618|
CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS
|(Amounts in thousands, except share and per share data)|
|Three Months Ended
|Revenue from collaborative and other agreements||$||7,093||$||15,184|
|Product revenue, net||3,580||887|
|Revenue from government agreements||428||810|
|Costs and expenses:|
|Cost of product sales||48||17|
|Research and development||61,438||53,121|
|Selling, general and administrative||16,253||15,036|
|Total costs and expenses||77,739||68,174|
|Loss from operations||(66,638||)||(51,293||)|
|Other comprehensive income (loss):|
|Unrealized gain (loss) on investments||(222||)||18|
|Comprehensive income (loss)||$||(66,665||)||$||(51,254||)|
|Basic and diluted net loss per common share||$||(1.08||)||$||(0.90||)|
|Basic and diluted weighted average common shares outstanding||61,324,163||57,202,846|
About MacroGenics, Inc.
Cautionary Note on Forward-Looking Statements
Any statements in this press release about future expectations, plans and prospects for
Source: MacroGenics, Inc.