UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d) of the
Securities Exchange Act of 1934
Date of report (Date of earliest event reported): September 16, 2024
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Registrant's telephone number, including area code: (301 ) 251-5172
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Emerging growth company ☐
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| Item 8.01 | Other Events. | ||||||||||||||||
On September 15, 2024, MacroGenics, Inc. (the “Company”) issued a press release announcing updated efficacy and safety data related to its Phase 2 TAMARACK clinical trial of vobramitamab duocarmazine in metastatic castration-resistant prostate cancer (the “Press Release”). The Company included the updated efficacy and safety data in a poster presentation at the European Society for Medical Oncology (“ESMO”) Congress, taking place in Barcelona, Spain from September 13-17, 2024.
As announced in the Press Release, the Company also hosted an investor conference call on September 16, 2024 in which the Company presented a review of the TAMARACK Phase 2 data and also provided a general corporate update (the “Post-ESMO Conference Call Presentation”).
The full text of the Press Release is attached as Exhibit 99.1 to this Current Report on Form 8-K and is incorporated by reference herein. In addition, a copy of the Post-ESMO Conference Call Presentation is attached as Exhibit 99.2 to this Current Report on Form 8-K and is incorporated by reference herein.
| Item 9.01 | Financial Statements and Exhibits | ||||||||||||||||
(d) Exhibits. | |||||||||||||||||
| Exhibit Number | Description of Exhibit | ||||||||||||||||
| 104 | Cover Page Interactive Data File (formatted as Inline XBRL). | ||||||||||||||||
SIGNATURE
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
Date: September 16, 2024 | MACROGENICS, INC. | |||||||||||||||||||||||||
By: /s/ Jeffrey Peters Jeffrey Peters Senior Vice President and General Counsel | ||||||||||||||||||||||||||
Exhibit 99.1
MacroGenics Announces Updated Efficacy & Safety Data from TAMARACK Phase 2 Study of Vobra Duo in mCRPC Patients at ESMO Congress 2024
•Encouraging antitumor activity demonstrated with vobra duo as measured by 6-month landmark rPFS rate and ORR
•Patients remained on vobra duo through a median of 6 doses (ranging up to 12), representing an extension of treatment duration as compared to Phase 1 mCRPC dose expansion cohort
•Company expects to have mature median rPFS no later than early 2025
•MacroGenics to host an investor call to review key data presented at ESMO and provide a general corporate update on Monday, September 16, 2024, at 8:00 a.m. ET
ROCKVILLE, MD., September 15, 2024 (GLOBE NEWSWIRE) — MacroGenics, Inc. (NASDAQ: MGNX), a biopharmaceutical company focused on discovering, developing, manufacturing and commercializing innovative antibody-based therapeutics for the treatment of cancer, today presented updated efficacy and safety results from the TAMARACK Phase 2 study of vobramitamab duocarmazine (vobra duo), an antibody-drug conjugate (ADC) that targets B7-H3, for patients with metastatic castration-resistant prostate cancer (mCRPC). The data were featured in a poster presentation at the European Society for Medical Oncology (ESMO) Congress, taking place in Barcelona, Spain from September 13-17, 2024.
“A key reason for conducting the TAMARACK study was to test the hypothesis that we could improve upon the duration of vobra duo treatment observed in the Phase 1 study by reducing the starting dose from 3.0 mg/kg to either 2.0 or 2.7 mg/kg and increasing the dosing interval from every three weeks to every four weeks. In doing so, our aim was to improve safety and tolerability, extend the treatment duration and achieve improved rPFS as compared to the result in our Phase 1 mCRPC dose expansion cohort,” said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. “We believe that these latest results from TAMARACK continue to demonstrate that vobra duo is an active drug in prostate cancer. Ultimately, our path forward for the molecule will depend on the final safety and efficacy data, including mature median rPFS, which we expect to have in hand no later than early 2025. We expect to make decisions about potential future development in the context of a competitive treatment landscape
assessment, resource allocation across our clinical portfolio and potential partnering opportunities for vobra duo.”
TAMARACK Study Demographics
The abstract submitted to ESMO was based on a data cut-off as of April 12, 2024; updated data based on a cut-off date of July 9, 2024, are included below and are reported in the Company’s poster presentation at ESMO.
The TAMARACK trial enrolled a total of 181 participants, with 176 participants receiving at least one dose of vobra duo at either 2.0 mg/kg q4W (n=90) or 2.7 mg/kg q4W (n=86). As of the data cut-off date, 23 and 16 participants remained on treatment in the 2.0 mg/kg and 2.7 mg/kg cohorts, respectively. While mCRPC study participants are no longer being dosed in the study, participants continue to be monitored for adverse events, disease progression, and survival.
Baseline Characteristics:
•Enrolled study participants had a median age of 70 years (range, 35-89).
•88 Study participants (48.6%) had an ECOG performance status of 1 or 2.
•30 Study participants (16.6%) had visceral disease at baseline, with liver or lung disease in 25 participants (13.8%).
•81 Study participants (44.8%) had measurable disease at baseline, and 97 (53.6%) had received prior taxane.
•Both treatment arms were well-balanced across most baseline characteristics, including prior use of taxanes, androgen receptor axis-targeted (ARAT) treatment, poly-ADP ribose polymerase (PARP) treatment, and baseline PSA.
TAMARACK Efficacy Results as of July 9, 2024 Cut-off Date
Overall, the Company believes that the results to date from the TAMARACK study indicate antitumor activity associated with vobra duo in mCRPC as demonstrated by the protocol-specified primary endpoint of landmark 6-month radiographic progression-free survival (rPFS) rate, as well as other measures of tumor response.
•In the intent-to-treat (ITT) population, 6-month rPFS rate was 69% for the 2.0 mg/kg arm (95% CI, 57-79) and 70% for the 2.7 mg/kg arm (95% CI, 58-79).
•Landmark 6-month rPFS rates were consistent across taxane-naïve study participants (ranging from 66-82%) and taxane pre-treated study participants (ranging from 60-73%), regardless of treatment arm.
•Although immature, with only 65 PFS events (35.9%) as of the data cut-off, median rPFS was approximately 8.5 months for the 2.0 mg/kg cohort (95% CI, 7.2-11.2) and 7.5 months for the 2.7 mg/kg cohort (95% CI, 7.2-10.6). Because these results were immature as of the cutoff date, they are likely to change as additional events accrue.
Tumor response rates
•Out of 45 RECIST-response evaluable patients in the 2.0 mg/kg arm, the confirmed objective response rate (ORR) was 20.0% (n=9) and the unconfirmed ORR was 26.7% (n=12).
•Out of 32 RECIST-response evaluable patients in the 2.7 mg/kg arm, the confirmed ORR was 40.6% (n=13) and the unconfirmed ORR was 46.9% (n=15).
•Confirmed ORR was comparable between taxane-naïve study participants (26.7%, n=12/45) and taxane pre-treated study participants (17.5%, n=11/63), regardless of treatment arm.
•Tumor responses did not appear to correlate with baseline B7-H3 expression based on archival tissue samples of mixed age.
TAMARACK Safety Results as of July 9, 2024 Cut-off Date
Overall summary of adverse events (AEs)
•In the 2.0 mg/kg cohort, 65.6% of study participants (n=59) experienced a Grade ≥3 treatment-emergent AE (TEAE); this cohort had a discontinuation rate of 25.6% (n=23) and a dose reduction rate of 50.0% (n=45) due to TEAEs.
•In the 2.7 mg/kg cohort, 62.8% of study participants (n=54) experienced a Grade ≥3 TEAE; this cohort had a discontinuation rate of 38.4% (n=33) and a dose reduction rate of 54.7% (n=47) due to TEAEs.
•The most common (occurring in ≥20% of study participants) all-grade TEAEs were: asthenia, edema peripheral, decreased appetite, nausea, pleural effusion, diarrhea, fatigue, constipation, anemia, palmar-plantar erythrodysesthesia (PPE, or hand-foot syndrome), neutropenia, and stomatitis. The majority of TEAEs with a ≥10% incidence rate in either treatment arm was limited to Grade 1/2 events.
•Rates of pleural effusion, pericardial effusion, and PPE for both the 2.0 mg/kg cohort (28.8%, 13.3%, 18.9%, respectively) and the 2.7 mg/kg cohort (44.2%, 17.5%, 28%, respectively) decreased compared to the Phase 1 mCRPC dose expansion cohort (48.8%, 17.1%, 46.3%, respectively), despite an increased median number of doses of vobra duo administered on TAMARACK.
•Eight fatal treatment-related AEs as assessed by the treating physician: five in the 2.0 mg/kg cohort and three in the 2.7mg/kg cohort. These include three events of pneumonitis, and one event each of cardiac failure, stress cardiomyopathy, ventricular fibrillation, pleural effusion, and gastrointestinal hemorrhage.
•Rates of treatment-related AEs (including all grades and Grade ≥3) and treatment-related severe AEs were similar between taxane-naïve and taxane pre-treated study participants.
Tolerability findings
•In the 2.0 mg/kg cohort, 25.6% of study participants (n=23) remained on study drug as of July 9, 2024. Study participants received a median number of 6 doses (range, 1-11), with a median dose intensity (calculated as a percentage of the total planned dose that was administered) of 92.6% (range, 64.2-106.1%).
•In the 2.7 mg/kg cohort, 18.6% of study participants (n=16) remained on study drug as of the data cut-off date. Study participants received a median number of 6 doses (range, 1-12), with a median dose intensity of 81.7% (range, 40.5-104.3%).
•Taxane-naïve study participants experienced higher rates of dose reductions due to TEAEs (62.7%) and dose interruptions due to TEAEs (70.7%) compared to taxane pre-treated study participants (44.6% and 43.6%, respectively).
ESMO Poster Presentation
Title: TAMARACK: Randomized Phase 2 trial of the B7-H3 targeting antibody drug conjugate (ADC) vobramitamab duocarmazine (vobra duo) in metastatic castration-resistant prostate cancer (mCRPC)
Presenter / Lead Author: Johann de Bono, M.D., M.Sc., Ph.D., FRCP, FMedSci, Division of Clinical Studies, Royal Marsden Hospital Institute of Cancer Research, Sutton, UK
Presentation ID: 1654P
Session Date: Sunday, September 15, 2024
Poster Display Time: 9:00 a.m. – 5:00 p.m. CEST
The poster presentation is available for download under "Events & Presentations" in the Investor Relations section of MacroGenics’ website at http://ir.macrogenics.com/events.cfm.
Conference Call
The Company will host a conference call to discuss the TAMARACK poster data and provide a general corporate update on Monday, September 16, 2024, at 8:00am ET. The call will be led by
Scott Koenig, M.D., Ph.D., President and Chief Executive Officer; Stephen Eck, M.D., Ph.D., Senior Vice President - Chief Medical Officer; and Jim Karrels, Senior Vice President - Chief Financial Officer.
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 the Company's 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 the Company's website for 30 days following the call.
About Vobra Duo and the TAMARACK Study
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. The TAMARACK Phase 2 study of vobra duo is being conducted in participants with 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).
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 and the MacroGenics logo 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 and regulatory plans for the Company’s therapeutic candidates, expected timing of the release of final safety and efficacy data, including mature median rPFS 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 timing and results of mature median radiographic progression-free survival, other efficacy and safety data 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; costs of litigation and the failure to successfully defend lawsuits and other claims against us; 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
Developing Breakthrough Biologics, Life-changing Medicines® Post-ESMO Conference Call September 16, 2024
2 Legal Notices The information in this slide deck is current as of September 16, 2024, unless otherwise noted, and is qualified in its entirety by reference to MacroGenics’ Annual, Quarterly and Current Reports filed with the SEC. MacroGenics undertakes no obligation to update any of the information herein. Cautionary Note on Forward-Looking Statements Any statements in this presentation about future expectations, plans and prospects for MacroGenics (“Company”), including statements about the Company’s strategy, future operations, clinical development of and regulatory plans for the Company’s therapeutic candidates, expected timing of the release of final safety and efficacy data, including mature median rPFS 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 timing and results of mature median radiographic progression-free survival, other efficacy and safety data 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; costs of litigation and the failure to successfully defend lawsuits and other claims against us; 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. Trademarks DART, TRIDENT, MacroGenics, the MacroGenics logo and MARGENZA are trademarks or registered trademarks of MacroGenics, Inc. All third-party trademarks used herein are registered trademarks of their respective owners. Investigational Agents The safety and efficacy of investigational agents and/or investigational uses of approved products have not been established. September 16, 2024
3 Conference Call Agenda Introduction Scott Koenig, M.D., Ph.D. – President and CEO, MacroGenics Updated TAMARACK Study Results Stephen Eck, M.D. – SVP, Clinical Development and Chief Medical Officer Pipeline Update Scott Koenig, M.D., Ph.D. Q&A September 16, 2024
4 Conference Call Agenda Introduction Scott Koenig, M.D., Ph.D. – President and CEO, MacroGenics Updated TAMARACK Study Results Stephen Eck, M.D. – SVP, Clinical Development and Chief Medical Officer Pipeline Update Scott Koenig, M.D., Ph.D. Q&A September 16, 2024
5 Phase 2 TAMARACK Study: Hypothesis & Key Findings Hypothesis • Continued encouraging antitumor activity as measured by ORR and PSA response rate • Extended duration of therapy observed compared to Phase 1 study as measured by median number of doses received • Improvement in safety and tolerability Achieved goal of extending treatment duration and response to therapy while maintaining / improving anti-tumor activity Vobra duo safety could be improved while maintaining efficacy observed in Phase 1 study by: • Reducing starting dose • Increasing dosing interval Key considerations informing potential vobra duo next steps Evaluation of mature median rPFS Assessment of competitive landscape Resource allocation across clinical portfolio (maturity expected no later than early 2025) Input from external KOLS Potential partnering opportunities Presented at ESMO 2024; Data Cut-off: July 9, 2024 As of July 9, 2024 data cutoff September 16, 2024
6 Conference Call Agenda Introduction Scott Koenig, M.D., Ph.D. – President and CEO, MacroGenics Updated TAMARACK Study Results Stephen Eck, M.D. – SVP, Clinical Development and Chief Medical Officer Pipeline Update Scott Koenig, M.D., Ph.D. Q&A September 16, 2024
7 Experimental Arm A Vobramitamab duocarmazine 2.0 mg/kg Q4W Experimental Arm B Vobramitamab duocarmazine 2.7 mg/kg Q4W R 1:1 Study Participants Enrolled N=91 Primary Endpoint: rPFS Key Secondary Endpoints: AEs, PSA outcomes, ORR, DoR, SSEs, PK, ADA, nAb (a) Participants who received an additional taxane or second ARAT (androgen receptor axis-targeted agent [abiraterone, enzalutamide or apalutamide]) for <60 days as bridging therapy while awaiting lutetium-177 vipivotide tetraxetan are also eligible. Other prior chemotherapy for prostate cancer is not allowed. mCRPC=metastatic castration-resistant prostate cancer; ORR=objective response rate; PSA=prostate-specific antigen; Q4W=every 4 weeks; R=randomize; rPFS=radiographic progression-free survival. Vobra Duo: mCRPC Phase 2 Study Design Summary (TAMARACK) Stratification Factors: • Visceral disease (yes vs. no) • Prior taxane (yes vs. no) • Region (US/Canada vs. other) Key Eligibility Criteria: • mCRPC • One prior ARAT • Up to one prior docetaxel- containing regimen(a) • ≤ 3 Prior lines of therapy for mCRPC September 16, 2024 Study Participants Enrolled N=90
8 Study Participants Flow (a) Excludes 3 study participants not dosed with vobra duo who were originally assigned to control arm on earlier version of protocol. These study participants are excluded from all analyses in this presentation. (b) PSA-evaluable population includes study participants who received at least 1 dose of study treatment, had baseline PSA ≥2 ng/mL, and ≥1 postbaseline PSA measurement. (c) All study participants who received ≥1 dose of vobra duo, with baseline and postbaseline target lesion measurements (by RECIST v1.1). ITT=intent-to-treat. • Randomized, N=91 o Treated, N=90 o Not treated, N=1 – Withdrew consent, N=1 • Randomized, N=90 o Treated, N=86 o Not treated, N=4 – Withdrew consent, N=4 • ITT, N=91 • Safety, N=90 • PSA evaluable, N=82(b) • RECIST evaluable with measurable(c) disease at baseline, N=45 • ITT, N=90 • Safety, N=86 • PSA evaluable, N=71(b) • RECIST evaluable with measurable(c) disease at baseline, N=32 • On treatment, N=23 • Discontinued treatment, N=67 o In follow-up, N=38 o Completed follow-up, N=10 o Death, N=14 o Lost to follow-up, N=1 o Withdrew consent, N=4 • On treatment, N=16 • Discontinued treatment, N=70 o In follow-up, N=40 o Completed follow-up, N=10 o Death, N=11 o Lost to follow-up, N=1 o Withdrew consent, N=8 Randomized 1:1, N=181(a) Assessed for Eligibility, N=249 Vobra duo 2.0 mg/kg Q4W Vobra duo 2.7 mg/kg Q4WEn ro llm en t Al lo ca tio n Fo llo w -u p An al ys is Presented at ESMO 2024; Data Cut-off: July 9, 2024 September 16, 2024
9 Demographics and Baseline Characteristics (a) All randomized study participants, including the study participants not treated. PARP=poly (ADP-ribose) polymerase. Parameter Vobra duo 2.0 mg/kg Q4W N=91 Vobra duo 2.7 mg/kg Q4W N=90 Median (range) age, years 71 (46-89) 69 (35-86) ECOG PS, n (%) 0 42 (46.2) 51 (56.7) 1 48 (52.7) 37 (41.1) 2 1 (1.1) 2 (2.2) Disease status at first diagnosis, n (%) Local resectable 28 (30.8) 37 (41.1) Locally advanced unresectable 12 (13.2) 9 (10.0) Metastatic 51 (56.0) 44 (48.9) Type of disease progression at study entry, n (%) Radiographic progression of measurable disease 43 (47.3) 31 (34.4) Radiographic progression of bone disease (in >2 new bone lesions) 33 (36.3) 41 (45.6) PSA progression only 24 (26.4) 25 (27.8) PSA progression with any other type of progression 39 (42.9) 32 (35.6) Study participants with visceral disease, n (%) 15 (16.5) 15 (16.7) Study participants with prior taxane, n (%) 48 (52.7) 49 (54.4) Study participants with prior PARP, n (%) 6 (6.6) 8 (8.9) Number of prior ARAT, n (%) 1 82 (90.1) 84 (93.3) >1 9 (9.9) 6 (6.7) Baseline PSA n 89 85 Mean (standard deviation), ng/mL 180.5 (542.60) 182.6 (433.06) Median (range), ng/mL 26.4 (0.8-3447.0) 24.7 (0.2-2778.0) PSA ≥2 ng/mL, n (%) 83 (91.2) 74 (82.2) ITT population, N=181(a) Presented at ESMO 2024; Data Cut-off: July 9, 2024 September 16, 2024
10 rPFS per Investigator by PCWG3 Presented at ESMO 2024; Data Cut-off: July 9, 2024 ITT population, N=181 100 90 80 70 60 50 40 30 20 10 0 0 2 4 6 8 10 12 No. at risk Vobra duo 2.0 mg/kg Q4W 91 81 67 31 17 2 0 Vobra duo 2.7 mg/kg Q4W 90 77 65 34 15 3 0 rP FS p ro ba bi lit y (% ) Time from randomization (months) Vobra duo 2.0 mg/kg Q4W, N=91 Vobra duo 2.7 mg/kg Q4W, N=90 Events, n (%) 30 (33.0) 35 (38.9) rPFS at 6 months (95% CI), % 69 (57-79) 70 (58-79) + CENSORED September 16, 2024 (a) Company anticipates having final median rPFS no later than early 2025 based on collection of events no later than January 2025 (as per study design). PCWG3=Prostate Cancer Working Group 3 Although immature(a) and subject to change, with only 65 (35.9%) rPFS events as of data cut-off date (July 9, 2024), median rPFS was: • 8.5 mos. (95% CI, 7.2-11.2) on 2.0 mg/kg arm • 7.5 mos. (95% CI, 7.2-10.6) on 2.7 mg/kg arm
11 Tumor and PSA Responses (a) All study participants who received ≥1 dose of vobra duo, with baseline and postbaseline target lesion measurements (by RECIST v1.1). (b) All study participants who received ≥1 dose of vobra duo, with a baseline PSA ≥2 ng/mL and ≥1 postbaseline PSA measurement. NE=not evaluable; SD=stable disease. Vobra duo 2.0 mg/kg Q4W Vobra duo 2.7 mg/kg Q4W RECIST response-evaluable population w/baseline measurable disease(a) N=45 N=32 Best overall response (confirmed), n (%) CR 0 1 (3.1) PR 9 (20.0) 12 (37.5) SD 30 (66.7) 15 (46.9) PD 5 (11.1) 2 (6.3) NE 1 (2.2) 2 (6.3) Confirmed ORR (CR + PR), n (%) 9 (20.0) 13 (40.6) Confirmed + unconfirmed ORR, n (%) 12 (26.7) 15 (46.9) Median (range) DOR of confirmed RECIST responders, months [n] 4.9 (1.94-6.47) [9] NE (1.54-9.46) [13] PSA response-evaluable population(b) N=82 N=71 PSA50 response (confirmed), n (%) 37 (45.1) 28 (39.4) PSA50 response (confirmed + unconfirmed), n (%) 41 (50.0) 37 (52.1) Median (range) DOR of confirmed PSA50 responders, months [n] NE (0.95-9.23) [37] NE (0.95-9.49) [28] Presented at ESMO 2024; Data Cut-off: July 9, 2024 September 16, 2024
12 Best % Change in Target Lesions From Baseline per Investigator (a) All study participants who received ≥1 dose of vobra duo, with baseline and postbaseline target lesion measurements (by RECIST v1.1). cCR=confirmed complete response; CR=complete response; cPR, confirmed partial response; PR, partial response. Presented at ESMO 2024; Data Cut-off: July 9, 2024 RECIST response-evaluable population with measurable disease, N=77(a) Be st % c ha ng e of t ar ge t le si on fr om b as el in e, N = 44 Study participants with measurable disease at baseline, N=45 Confirmed ORR (cCR + cPR) 9/45 (20.0%) Unconfirmed ORR (CR + PR) 12/45 (26.7%) −100 100 90 80 70 60 50 40 30 20 10 0 −10 −20 −40 −60 −80 −30 −50 −70 −90 Archival biopsy B7-H3 membrane H-score category 0 >0-100 >100-200 >200-300 Unknown ^ Off-chart % change >100% * Treatment ongoing 1 of the 45 study participants with measurable disease at baseline did not have any postbaseline tumor assessment. Vobra Duo 2.0 mg/kg Q4W Be st % c ha ng e of t ar ge t le si on fr om b as el in e, N = 30 Vobra Duo 2.7 mg/kg Q4W Study participants with measurable disease at baseline, N=32 Confirmed ORR (cCR + cPR) 13/32 (40.6%) Unconfirmed ORR (CR + PR) 15/32 (46.9%) −100 100 90 80 70 60 50 40 30 20 10 0 −10 −20 −40 −60 −80 −30 −50 −70 −90 2 of the 32 study participants with measurable disease at baseline did not have any postbaseline tumor assessment. * Treatment ongoing September 16, 2024 ORRs across both dosing cohorts indicate robust anti-tumor activity
13 Treatment Exposure and Reason for Treatment Discontinuation (a) Total dose intensity is calculated as total dose administered / total planned dose × 100. Total planned dose = assigned dose at randomization * baseline weight * [(last dose date – first dose date) / 28 + 1] rounded to nearest whole number. (b) Expansion cohort data from Phase 1 study (NCT03729596) of vobra duo in men with mCRPC who had progressed after 1 prior line of chemotherapy for metastatic disease and no more than 2 prior lines of antihormonal therapy; participants were required to have PSA ≥2 ng/mL and documented progressive disease per PCWG2 criteria; data as of final cut- off date of August 3, 2023. TAMARACK vobra duo 2.0 mg/kg Q4W TAMARACK vobra duo 2.7 mg/kg Q4W CP-MGC018-01 vobra duo 3.0 mg/kg Q3W(b) Treated with any study treatment, n 90 86 41 Treatment discontinued, n (%) 67 (74.4) 70 (81.4) 41 (100) Adverse event 22 (24.4) 31 (36.0) 15 (36.6) Death 2 (2.2) 2 (2.3) 0 Physician decision 5 (5.6) 2 (2.3) 0 Progressive disease 28 (31.1) 28 (32.6) 24 (58.5) Subject decision/withdrew consent 10 (11.1) 7 (8.1) 2 (4.9) Treatment ongoing, n (%) 23 (25.6) 16 (18.6) 0 Mean (standard deviation) number of doses 6.1 (2.35) 5.5 (2.39) 5.0 (2.98) Median (range) number of doses 6 (1-11) 6 (1-12) 4.0 (1.0-15.0) Median (range), duration study treatment, months 6.4 (1.0-11.1) 6.7 (1.0-12.9) 4.2 (2.1-15.0) Median (range) dose intensity,(a) % 92.6 (64.2-106.1) 81.7 (40.5-104.3) 66.4 (26.7-102.9) Presented at ESMO 2024; Data Cut-off: July 9, 2024 September 16, 2024 Results indicate improve- ment in duration of therapy for vobra duo in TAMARACK compared to that of Phase 1 mCRPC expansion cohort (i.e., median of 6 vs. 4 doses, respectively)
14 Overall Summary of TEAEs on TAMARACK and CP-MGC018-01 (a) Includes events with causality assessments of “possible,” “probable,” or “definite,” per investigator. (b) Expansion cohort data from Phase 1 study (NCT03729596) of vobra duo in men with mCRPC who had progressed after 1 prior line of chemotherapy for metastatic disease and no more than 2 prior lines of antihormonal therapy; participants were required to have PSA ≥2 ng/mL and documented progressive disease per PCWG2 criteria; data as of final cut-off date of August 3, 2023. SAE=serious adverse event. AEs, n (%) Vobra duo 2.0 mg/kg Q4W N=90 Vobra duo 2.7 mg/kg Q4W N=86 CP-MGC018-01 3.0 mg/kg Q3W(b) N=41 Any TEAE 89 (98.9) 86 (100) 41 (100) Treatment-related AEs(a) 87 (96.7) 84 (97.7) 41 (100) Any grade ≥3 TEAE 59 (65.6) 54 (62.8) 33 (80.5) Grade ≥3 treatment-related AE(a) 42 (46.7) 45 (52.3) 32 (78.0) Any SAE 34 (37.8) 38 (44.2) 23 (56.1) Treatment-related SAEsa 23 (25.6) 24 (27.9) 19 (46.3) Fatal treatment-related AEs 5 (5.6) 3 (3.5) 2 (4.9) TEAEs resulting in vobra duo discontinuation 23 (25.6) 33 (38.4) 15 (36.6) TEAEs resulting in vobra duo dose reductions 45 (50.0) 47 (54.7) 28 (68.3) TEAEs resulting in vobra duo interruption 46 (51.1) 51 (59.3) 28 (68.3) Presented at ESMO 2024; Data Cut-off: July 9, 2024 September 16, 2024 Overall improvement in safety and tolerability in TAMARACK compared to that of Phase 1 mCRPC expansion cohort
15 (Safety population, N=176) (a) Includes one treatment-related pleural effusion event reported to be grade 3 but with a fatal outcome; site query to correct the discrepancy is pending. TEAEs Reported in ≥10% of Study Participants in Either Arm Presented at ESMO 2024; Data Cut-off: July 9, 2024 Asthenia – Pleural effusion(a) – Decreased appetite – Edema peripheral – Nausea – PPE syndrome – Stomatitis – Neutropenia – Fatigue – Diarrhea – Anemia – Constipation – Dyspnea – Conjunctivitis – Headache – Pericardial effusion – Pyrexia – Cough – Thrombocytopenia – Back pain – Insomnia – Dysgeusia – Abdominal pain – Dry eye – Lymphopenia – Infusion-related reaction – Platelet count decreased – Weight decreased – Dry skin – Atrial fibrillation – Rash – Arthralgia – Vomiting – Vobra Duo 2.0 mg/kg Q4W Vobra Duo 2.7 mg/kg Q4W % of study participants with TEAEs 51.1% 59.3% 28.9% 44.2% 35.6% 39.5% 36.7% 37.2% 35.6% 30.2% 18.9% 27.9% 13.3% 26.7% 18.9% 25.6% 26.7% 23.3% 27.8% 23.3% 23.3% 23.3% 24.4% 23.3% 10.0% 19.8% 12.2% 19.8% 13.3% 17.4% 13.3% 17.4% 13.3% 15.1% 7.8% 15.1% 6.7% 15.1% 10.0% 14.0% 3.3% 11.6% 11.1% 11.6% 4.4% 11.6% 12.2% 10.5% 4.4% 10.5% 4.4% 10.5% 8.9% 10.5% 11.1% 9.3% 18.9% 9.3% 10.0% 8.1% 10.0% 8.1% 13.3% 8.1% 15.6% 5.8% Grade 4 Grade 3 Grade 2 Grade 1 Grade 5 100 90 80 70 60 50 40 30 20 10 0 10 20 30 40 50 60 70 80 90 100 September 16, 2024
16 Select TEAEs by Grade and Dose in TAMARACK and CP-MGC018-01 (a) Includes one treatment-related pleural effusion event reported to be grade 3 but with a fatal outcome; site query to correct the discrepancy is pending. (b) Expansion cohort data from Phase 1 study (NCT03729596) of vobra duo in men with mCRPC who had progressed after 1 prior line of chemotherapy for metastatic disease and no more than 2 prior lines of antihormonal therapy; participants were required to have PSA ≥2 ng/mL and documented progressive disease per PCWG2 criteria; data as of final cut-off date of August 3, 2023. TAMARACK safety population, N=176; CP-MGC018-01 safety population, N=41 Presented at ESMO 2024; Data Cut-off: July 9, 2024 10.0 13.3 20.9 4.7 12.8 26.8 24.4 14.4 12.2 5.6 18.6 9.3 14.0 22.0 14.6 17.1 2.2 1.1 4.7 2.3 1.2 2.4 4.9 2.2 1.2 0 5 10 15 20 25 30 35 40 45 50 Grade 1 Grade 2 Grade 3 Grade 4 St ud y pa rt ic ip an ts (% ) Grade 4 Grade 3 Grade 2 Grade 1 TAMARACK CP-MGC018-01(b) 2.0 mg/kg Q4W median number of doses: 6 2.7 mg/kg Q4W median number of doses: 6 3.0 mg/kg Q3W median number of doses: 4 Pleural effusion Pericardial effusion PPE syndrome Pleural effusiona Pericardial effusion PPE syndrome Pleural effusion Pericardial effusion PPE syndrome September 16, 2024
17 Summary As of July 9, 2024 data cutoff • Data demonstrated vobra duo’s antitumor activity by ORR and PSA response rate • Anticipate having final TAMARACK median rPFS no later than early 2025 • Company believes it has better understanding of vobra duo’s overall safety and tolerability and is considering ways to further improve molecule’s safety as it awaits final median rPFS • Through dose reduction and increase in dosing interval, events of neutropenia, anemia, thrombocytopenia, pleural effusion and PPE syndrome improved compared to Phase 1 dose expansion in mCRPC; also, on average, TAMARACK study participants stayed on treatment longer than did those in Phase 1 • Company is considering exploring whether adverse events associated with prolonged exposure to vobra duo could be mitigated by strategies such as further increasing dosing intervals or utilizing loading doses Presented at ESMO 2024; Data Cut-off: July 9, 2024 September 16, 2024
18 Conference Call Agenda Introduction Scott Koenig, M.D., Ph.D. – President and CEO, MacroGenics Updated TAMARACK Study Results Stephen Eck, M.D. – SVP, Clinical Development and Chief Medical Officer Pipeline Update Scott Koenig, M.D., Ph.D. Q&A September 16, 2024
19 Deep and Differentiated Proprietary Pipeline with Retained Commercial Rights The safety and efficacy of investigational agents and/or investigational uses of approved products have not been established. Pipeline reflects current status of each program or most recently completed phase of development. (a) The “Help Elucidate & Attack Longitudinally” (HEAT) study is an investigator-sponsored trial. (b) MacroGenics currently has no active/ongoing tebotelimab studies. September 16, 2024 Program (Target) Potential Indication(s) Modality/ Platform Preclinical Phase 1 Phase 2 Phase 3 Partner / Sponsor Vobramitamab Duocarmazine (B7-H3) mCRPC Study ADC Multiple Solid Tumors (+lorigerlimab) ADC + DART® Lorigerlimab (PD-1 × CTLA-4) mCRPC (+docetaxel) Study DART Enoblituzumab (B7-H3) Neo-adj. Prostate Cancer HEAT Study(a) Fc-optimized mAb Tebotelimab(b) (PD-1 × LAG-3) Solid Tumors & Heme Malignancies DART MGC026 (B7-H3) Multiple Solid Tumors ADC MGC028 (ADAM9) Multiple Solid Tumors ADC
20 The safety and efficacy of investigational agents and/or investigational uses of approved products have not been established. Pipeline reflects current status of each program or most recently completed phase of development. (a) MacroGenics entered risk-sharing collaboration with Eversana in November 2020, under which MacroGenics books U.S. sales and Eversana leads execution of U.S. commercialization of MARGENZA. For all other currently partnered programs for which a license option has been exercised, the partner would book any future worldwide sales, if approved, and MacroGenics would be entitled to receive milestones and royalties. Partnered Programs: Potential Future Cash Flow & Platform Validation September 16, 2024 $435M Non-dilutive funding achieved since mid-2022 Program (Target) Potential Indication(s) Modality/ Platform Preclinical Phase 1 Phase 2 Phase 3 Marketed Partner MARGENZA® (HER2) HER2+ Metastatic Breast Cancer Fc-optimized mAb ZYNYZ® (PD-1) Merkel Cell Carcinoma mAb Squamous Cell Anal Carcinoma mAb Non-Small Cell Lung Cancer mAb TZIELD® (CD3) Stage 2 “At Risk” T1D mAb Stage 3 “Early Onset” T1D mAb MGD024 (CD123 × CD3) CD123+ Heme Malignancies DART Exclusive Option Bispecific (Undisclosed) Multiple Solid Tumors DART/TRIDENT® (a)
21 Multiple data catalysts Studies: Experience in combining novel targets with differentiated drug- linker technology Flexible platforms with clinical and/or partner validation Three approved products generated from our pipeline(a) fuel potential revenue $140M Cash as of 6/30/24, plus $100M in milestones subsequently received from Incyte, and other anticipated and potential future payments, should provide cash runway into 2026 Unique Capabilities to Develop Next Generation Antibodies for Treating Cancer (a) TZIELD® was sold to Provention Bio (Sanofi) and is marketed by Sanofi; ZYNYZ™ was licensed to, and is marketed by, Incyte. (b) The “Help Elucidate & Attack Longitudinally” (HEAT) neo-adjuvant prostate cancer study is an investigator-sponsored trial. September 16, 2024 Multiple Phase 2 Programs in Prostate Cancer Broad Capabilities for Drug Conjugates Proprietary Platforms for Multispecifics Proven R&D Track Record Well Funded to Deliver on Plan HEAT(b)
22 Conference Call Agenda Introduction Scott Koenig, M.D., Ph.D. – President and CEO, MacroGenics Updated TAMARACK Study Results Stephen Eck, M.D. – SVP, Clinical Development and Chief Medical Officer Pipeline Update Scott Koenig, M.D., Ph.D. Q&A September 16, 2024
23 Thank You! Jim Karrels – SVP, Chief Financial Officer 301-354-2681 | karrelsj@macrogenics.com Link to our latest presentations: http://ir.macrogenics.com/events.cfm www.macrogenics.com Investor Relations Inquiries: Business Development Inquiries: September 16, 2024 Eric Risser – Chief Operating Officer rissere@macrogenics.com Harish Krishnaswamy – Vice President, BD krishnaswamyh@macrogenics.com