CORPORATE UPDATE OCTOBER 2019 - BREAKTHROUGH BIOLOGICS, MACROGENICS, INC.
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®
Developing
Breakthrough Biologics,
Life-changing Medicines
Corporate Update
October 2019
Legal Notices
The information in this slide deck is current as of September 30, 2019, 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 these materials 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, 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 and other
statements containing the words “subject to”, "believe", “anticipate”, “plan”, “expect”, “intend”, “estimate”, “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: the uncertainties inherent in
the initiation and enrollment of future clinical trials, expectations of expanding ongoing clinical trials, availability and timing of data from ongoing
clinical trials, expectations for regulatory approvals, other matters that could affect the availability or commercial potential of the Company's
product candidates and other risks described in the Company’s filings with the Securities and Exchange Commission. In addition, the forward-
looking statements included in this presentation 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 “Breakthrough Biologics, Life-Changing Medicines” are trademarks or registered
trademarks of MacroGenics, Inc. The Incyte logo is a registered trademark of Incyte Corporation.
Investigational Agents
All Company product candidates described or mentioned herein are investigational and have not yet been approved for marketing by any
regulatory authority.
2 October 2019
Committed to Developing Life-changing Medicines
Innovative Combinatorial Approaches Resourced for Success
Nine immuno-oncology clinical candidates $272M Cash @ 06/30/19(a)
Multiple alliances with
Fc optimization platform to enhance antibodies’ immune activation
leading biopharma companies
Commercial scale GMP
Leading bispecific DART® platform to exploit multiple mechanisms
manufacturing facility
~380 Employees
Multi-program “franchises” around high-value targets (B7-H3, PD-1)
(Rockville, MD & SF Bay Area)
(a) Includes cash equivalents and marketable securities.
3 October 2019
Building Competitive Advantage Around Combinatorial Mechanisms
Tumor Destruction Restore T-Cell Function: Enhance T-cell Function:
and Antigen Presentation Checkpoint Inhibition T-Cell Recruitment
Complementary MOA’s Complementary MOA’s
MGA012
Flotetuzumab
Margetuximab
or Enoblituzumab
MGD013
TAA: tumor-associated antigen
4 October 2019
Broad Array of Engineered Antibody Formats
Engaging the Immune System to Target Cancer
Fc-Optimized Antibody Drug
Antibody DART/TRIDENT™ Molecules
Antibody Conjugate
Bivalent Bivalent Bivalent Bivalent Tetravalent Trivalent
Monospecific Monospecific Monospecific Bispecific Bispecific Trispecific
Fab Region
Fc Region
Key Features: • Enhance Fc-mediated • Leverage 3rd party • “Plug-and-play” multi-specific platforms
activity, incl. ADCC linker-payload tech
• Tailored half-life and avidity/valency to optimize product profile
(Synthon, Immunogen)
• Promote innate and • Broad range of modalities pursued:
adaptive immunity • Deliver potent anti-
tumor payload – Co-blockade of multiple checkpoint molecules
• Combine with – Redirect T-cell killing
checkpoint inhibitors
to augment activity – Tumor-directed co-stimulation
5 October 2019
Advancing Immuno-Oncology Pipeline
Retains major market commercial rights for 8 of 9 development candidates
Program (Target) Potential Indication Pre-IND Phase 1 Phase 2 Phase 3 Collaborator(s) Our Commercial Rights
Margetuximab (HER2) Breast “SOPHIA” Zai Lab, GC Pharma Worldwide, excluding South Korea
and Greater China
Gastric “MAHOGANY” (+MGA012)
Enoblituzumab (B7-H3) Solid Tumors (+MGA012) I-Mab Biopharma Worldwide, excluding Greater China
B7-H3
MGD009 (B7-H3 × CD3) Solid Tumors (+MGA012) — Worldwide
MGC018 (B7-H3)(a) Solid Tumors — Worldwide
MGA012 (PD-1) Solid Tumors Incyte(b) —
PD-1
MGD013 (PD-1 × LAG-3) Solid Tumors/Heme Mal. Zai Lab Worldwide, excluding Greater China
MGD019 (PD-1 × CTLA-4) Solid Tumors — Worldwide
Flotetuzumab (CD123 × CD3) AML — Worldwide
AML (+MGA012)
MGD007 (gpA33 × CD3) Colorectal (+MGA012) — Worldwide
“MGD” = DART “MGA” = Antibody “MGC” = ADC
(a) MGC018 is an antibody-drug conjugate (ADC) based on a duocarmycin payload with cleavable peptide linker that was licensed from Synthon Biopharmaceuticals.
(b) MacroGenics retains rights to develop its pipeline assets in combination w/MGA012 (INCMGA0012) and to manufacture a portion of global clinical and commercial supply needs of MGA012.
All Company product candidates described or mentioned herein are investigational and have not yet been approved for marketing by any regulatory authority.
6 October 2019
Core Product Candidates with Key Milestones Anticipated in 2019
Enhance Innate
Margetuximab Enoblituzumab Immune Function
(Anti-HER2 mAb) (Anti-B7-H3 mAb) through
Fc Optimization
Restore and
MGA012(a) MGD013 Flotetuzumab Redirect T-Cell
(Anti-PD-1 mAb) (PD-1 × LAG-3 DART) (CD123 × CD3 DART)
Function
(a) MacroGenics retains rights to develop its pipeline assets in combination with MGA012 (INCMGA0012) and to manufacture a portion of global clinical and commercial supply needs of MGA012.
7 October 2019
Margetuximab
Margetuximab: Anti-HER2 mAb Engineered to Enhance Activity of Immune System
Positive results from pivotal phase 3 study presented at ASCO 2019
• Inhibits HER2 signaling (similar to trastuzumab)
Function/
• Fc region engineered to engage innate and adaptive
MoA
immunity as mediators of anti-tumor activity
HER2 HER2
Pivotal • Ph. 3 SOPHIA study in HER2+ metastatic breast cancer
Fab
Region Clinical • Ph. 2/3 MAHOGANY study w/checkpoint inhibitor in
Studies HER2+ gastric cancer (initiated 3Q19)
• Ph. 3 SOPHIA study
‒ Positive PFS results reported ASCO 2019
Program
‒ 2nd Interim OS results exp. 4Q19, final OS in 2020
Fc Region
Status
• BLA submission in HER2+ mBC expected 4Q19
• Ph. 1 HER2+ gastric cancer data updated ESMO 2019
MacroGenics’
Retained • Global rights (excl. Greater China, South Korea)
Rights
Margetuximab is investigational and has not yet been approved for marketing by any regulatory authority
8 October 2019
Margetuximab
3rd/4th Line HER2+ Metastatic Breast Cancer Represents Attractive Entry Point
mBC Line of Therapy 1st Line 2nd Line 3rd/4th Line
Annual # of Patients(a) ~19,200 ~16,000 ~18,800
No consensus
Trastuzumab T-DM1
(lapatinib + capecitabine;
Standard of Care + pertuzumab (ado-trastuzumab
trastuzumab + different
+ taxane (docetaxel) emtansine)
chemo)
Median OS 56.5 months(b) 30.9 months(c) 15.8 months(d)
Median PFS 18.5 months(b) 9.6 months(c) 3.3 months(e)
ORR 80.2%(b) 43.6%(c) 8.6%
(a) US/EU5 Data from 9/13/18 Roche Virtual Late Stage Pipeline Event
(b) Baselga, et al. – CLEOPATRA Study Group; Perjeta package insert
(c) Verma, et al. – EMILIA Study Group; Kadcyla package insert
(d) Krop, et al., The Lancet (June 2017) – TH3RESA Study Group
(e) Krop, et al., The Lancet (May 2014) – TH3RESA Study Group
9 October 2019
Margetuximab
Phase 3 Study Comparing Margetuximab to Trastuzumab
SOPHIA clinical trial designed to support registration in 3rd/4th line HER2+ metastatic breast cancer
Arm 1
margetuximab +
HER2+ mBC chemotherapy
Investigator’s Choice of
1–3 Prior Treatment Lines Chemotherapy
in Metastatic Setting
(capecitabine, eribulin,
R 1:1 Randomization (N = 536)
(including prior treatment with gemcitabine or vinorelbine)
multiple other anti-HER2 agents)(a) Arm 2
trastuzumab +
chemotherapy
• Sequential primary endpoints: PFS and OS
− PFS and first interim OS analyses as of October 2018
− Second interim OS analysis planned at 270 events in 2H2019
− Final OS analysis planned at 385 events in 2020 Global sites: ~200
• Patients carrying CD16A (FcγRIIIa) 158F allele were pre-specified PFS (N=257, HR=0.67, α=0.05, power=90%)
exploratory subpopulation OS (N=385, HR=0.75, α=0.05, power=80%)
(a) All study patients had previously received trastuzumab and pertuzumab, and approximately 90% had previously received ado-trastuzumab emtansine.
10 October 2019Margetuximab
SOPHIA Ph. 3 Demonstrated Superiority to Trastuzumab in Primary PFS Endpoint
PFS prolonged in margetuximab arm vs. trastuzumab arm
PFS Primary Endpoint (ITT Population): Planned Exploratory Subpopulation (CD16A 158F Carriers):
24% Risk Reduction of Disease Progression 32% Risk Reduction of Disease Progression
Margetuximab Trastuzumab Margetuximab Trastuzumab
+ Chemotherapy + Chemotherapy + Chemotherapy + Chemotherapy
(n=266) (n=270) (n=221) (n=216)
# of events 130 135 # of events 103 112
Progression-free Survival (%)
Progression-free Survival (%)
Median PFS 5.8 months 4.9 months Median PFS 6.9 months 5.1 months
(95% CI) (5.52–6.97) (4.17–5.59) (95% CI) (5.55–8.15) (4.14–5.59)
HR=0.76 (95% CI, 0.59–0.98) P=0.033 HR=0.68 (95% CI, 0.52–0.90) P=0.005
Margetuximab + chemotherapy Margetuximab + chemotherapy
Trastuzumab + chemotherapy Trastuzumab + chemotherapy
Time from Randomization (Months) Time from Randomization (Months)
Margetuximab 221 157 84 42 21 8 6 4 2 0
Trastuzumab 216 129 62 30 11 2 2 1 1 1 1
ITT=Intent to Treat population: N=536. CD16A 158F Carriers=FF or FV Genotype. CI=confidence interval. HR=Hazard Ratio (by stratified Cox model). (Presented ASCO 2019)
11 October 2019Margetuximab
First Interim OS Analysis (Oct 2018): Preliminary Trend in Favor of Margetuximab
158 (41%) of 385 events needed for final OS analysis; second interim analysis at 270 events
OS Primary Endpoint Planned Exploratory
Margetuximab Trastuzumab Subpopulation Margetuximab Trastuzumab
(ITT Population) +Chemotherapy +Chemotherapy +Chemotherapy +Chemotherapy
(n=266) (n=270) (CD16A 158F Carriers) (n=221) (n=216)
# of events 78 80 # of events 59 65
Median OS 18.9 months 17.2 months Median OS 23.6 months 16.9 months
(95% CI) (16.16–25.07) (15.80–33.31) (95% CI) (16.56–NA) (15.41–20.53)
HR=0.95 (95% CI, 0.69–1.31) HR=0.82 (95% CI, 0.58–1.17)
NA=not achieved. ITT=Intent to Treat population. CI=Confidence Interval. HR=Hazard Ratio (by stratified Cox Model). (Presented ASCO 2019)
12 October 2019Margetuximab
Summary of Adverse Events (AEs)
Similar overall safety profiles
Margetuximab + Trastuzumab +
Chemotherapy (n=264) Chemotherapy (n=265)
Any grade AE, n (%) 258 (97.7) 255 (96.2)
Grade ≥3 AE, n (%) 138 (52.3) 128 (48.3)
SAE, n (%) 39 (14.8) 46 (17.4)
AE leading to treatment discontinuation, n (%) 8 (3.0) 7 (2.6)
AEs resulting in death,* n (%) 2 (0.8)† 2 (0.8)‡
Safety Population (randomized patients who received any study treatment): N=529.
*No AEs resulting in death were considered related to anti-HER2 study therapy.
†Pneumonia (n=1), pneumonia aspiration (n=1).
‡Pneumonia (n=1), acute kidney injury (n=1).
SAE=serious AE. (Presented ASCO 2019)
13 October 2019Margetuximab
AEs Regardless of Causality
Margetuximab + Trastuzumab +
Chemotherapy (n=264) Chemotherapy (n=265)
Most common AEs, n (%) All Grade* Grade ≥3† All Grade* Grade ≥3†
Fatigue 103 (39.0) 12 (4.5) 92 (34.7) 7 (2.6)
Nausea 81 (30.7) 3 (1.1) 84 (31.7) 1 (0.4)
Neutropenia 73 (27.7) 51 (19.3) 51 (19.2) 30 (11.3)
Diarrhea 59 (22.3) 6 (2.3) 62 (23.4) 5 (1.9)
Anemia 48 (18.2) 12 (4.5) 55 (20.8) 17 (6.4)
Neutrophil count decreased 32 (12.1) 22 (8.3) 35 (13.2) 25 (9.4)
Febrile neutropenia 8 (3.0) 8 (3.0) 12 (4.5) 12 (4.5)
AEs of special interest, n (%) All Grade Grade ≥3 All Grade Grade ≥3
Infusion-related reaction (IRR)‡ 34 (12.9) 4 (1.5) 10 (3.8) 0
Left ventricular dysfunction 6 (2.3) 3 (1.1) 7 (2.6) 1 (0.4)
Discontinuation due to IRRs, n (%) 3 (1.1) 2 (0.8) 0 0
Safety Population: N=529.
*Incidence ≥20% in either treatment group.
†Incidence ≥5% in either treatment group.
‡All patients received prior trastuzumab. In pivotal trials of trastuzumab, IRRs occurred in 21% to 40% of patients (US package insert). (Presented ASCO 2019)
14 October 2019Margetuximab
Capturing Full Potential of Margetuximab
Planned development strategy
3 Future Development Opportunities
• Neoadjuvant breast cancer
• Other HER2+ populations
2 Follow-on Indications
• 1st Line Gastric Cancer (w/checkpoints)
− Phase 2/3 MAHOGANY initiation in 3Q19
1 Potential Approval
• 3rd/4th line HER2+mBC (w/chemo)
− BLA submission planned in 4Q19
15 October 2019Margetuximab
Promising Activity in Advanced Gastric Cancer Patients in Phase 2 Study
33% ORR in HER2 3+ gastric cancer previously treated with chemotherapy
* ERBB2amp
* Treatment ongoing
Includes only patients evaluated per assay
* * * * * * * * * * * * * * * * * * *
* * * * * *
Gastric Cancer N ORR DCR mPFS mOS
HER2 IHC 3+(a) 55 32.7% (18/55) 69.1% (38/55) 4.70 (2.66, 7.49) 14.62 (10.55, NR)
IHC3+/PD-L1+(b) 23 52.2% (12/23) 82.6% (19/23) 5.52 (2.60, 13.90) 20.47 (8.08, NR)
Data cut-off July 10, 2019. Includes patients who received ≥1 margetuximab and pembrolizumab dose in expansion phase, and had baseline measurable disease and ≥1 post-baseline disease assessment.
(a) Immunohistochemistry (IHC) test gives score of 0 to 3+ that measures amount of HER2 receptor protein on surface of cells in cancer tissue sample. Score of 0 to 1+ is called “HER2 negative”, score of
2+ is called "borderline“, score of 3+ is called “HER2 positive.”
(b) “PD-L1 Positive” reflects Combined Positive Score (per standard FDA approved assay) ≥1% (PD-L1 tested on archival tissue by IHC; clone 22C3 pharmDx). (Presented ESMO 2019)
16 October 2019Margetuximab
Margetuximab + Anti-PD-1 Data in 2L Presents Opportunity to Advance to 1L
HER2+ gastric cancer benchmarks
1st Line 2nd Line 3rd Line
SOC SOC Ongoing Ph 2 Study Failed Ongoing Study
Trastuzumab + Ramucirumab Margetuximab + Pembrolizumab(c) Pembrolizumab(d)
Agent
(Study) Chemo(a) + Paclitaxel(b) (KEYNOTE-61) DS-8201(e)
(TOGA) (RAINBOW) IHC 3+ IHC 3+/PD-L1+ PD-L1+
ORR 47% 28% 33% 52% 15.8% 43%
Median PFS 6.7 mos. 4.4 mos. 4.7 mos. 5.5 mos. 1.5 mos. 5.6 mos.
Median OS 13.1 mos. 9.6 mos. 14.6 mos. 20.5 mos. 9.1 mos. 12.8 mos.
Overall: N/A
41% Neutropenia
≥ Grade 3 TRAEs 68% 20% 14% 48%
15% Hypertension
12% Fatigue
Gastric/GEJ
Patient Mix 80/20% 80/20% 100%/0% 70%/30% 80%/20%
SOC = Standard of Care
(a) Data from Herceptin package insert; Bang, et al., Lancet, 2010;
(b) Data from Cyramza package insert; Wilkes, et al., Lancet Oncology, 2014;
(c) Data presented at ESMO 2019; Grade 3 TRAE includes all GC and GEJ patients.
(d) Shitara, et al., 2018, Lancet;
(e) Shitara, et al., 2019, Lancet Oncol.
17 October 2019Margetuximab
MAHOGANY Phase 2/3 Study: Registration Path in 1L Gastric & GEJ Cancer
Global study initiated 3Q2019
Margetuximab + MacroGenics’ Anti-PD-1 (Chemo-free Regimen)
(add’l patients to support potential
Module A
(n=40) Accelerated Approval in the US )
HER2+ (IHC 3+) Primary
Single Experimental Arm: Go/ Single Experimental Arm:
and margetuximab + MGA012 No Go margetuximab + MGA012
Endpoint:
PD-L1+ (≥1% CPS) ORR
ORR and
Tolerability
Margetuximab + Chemo + MacroGenics’ Checkpoint Inhibitor
(n=50 per arm)
Standard of Care:
trastuzumab+ chemo (n=250 per arm)
Module B
HER2+ Experimental Arm #1: Standard of Care:
(IHC 3+ or margetuximab + chemo + MGA012 trastuzumab + chemo Primary
IHC 2+/FISH+) R Experimental Arm #2:
Futility
Analysis R Experimental Arm:
Endpoint:
OS
BLA
regardless of
margetuximab + chemo + MGD013 Assess marge + chemo + CPI*
PD-L1 status
Safety/efficacy of
Experimental Arm #3: Experimental
margetuximab + chemo Arms #1 and #2
MAHOGANY (Margetuximab in HER2-positive Gastric Cancer * Pending chronic tox study (if regimen with MGD013 is selected).
18 October 2019MGA012
MGA012: Development Across Eleven Clinical Studies
Global collaboration with Incyte
Function/ • Humanized, hinge-stabilized IgG4 mAb
MoA • Inhibits PD-1
PD-1 PD-1 • Eleven monotherapy or combo studies ongoing
Clinical • Initial monotherapy data projected in 2020(a)
Studies • Planned combination with margetuximab ± chemo in
Phase 2/3 MAHOGANY study in gastric cancer
Global Incyte
• $150M Upfront cash payment
Transaction
• Up to $750M in milestones ($15M received in 2018)
• Tiered royalties of 15-24% on future MGA012 sales
MacroGenics’ • Develop pipeline assets in combination with MGA012
Retained
• Manufacture portion of global MGA012 supply
Rights
(a) Ongoing studies in MSI-high endometrial cancer, Merkel cell carcinoma and anal cancer are potentially registration-directed.
19 October 2019MGA012
MGA012: Building a Pipeline within a Product
Comprehensive development program includes multiple registration-directed clinical studies
MSI-High Merkel Cell Anal Gastric Head & Neck
Endometrial Cancer Carcinoma Cancer Cancer Cancer
monotherapy monotherapy monotherapy + margetuximab ± chemo + enoblituzumab ± chemo
Data Expected Data Expected Data Expected Initiated 3Q19 Initiation Expected
2020 2020 2021 4Q19
• Additional benchmarking studies being conducted by Incyte
Non-small Cell Lung
Cancer ± Chemo Melanoma Renal Carcinoma Urothelial Cancer
Soft Tissue Endometrial
Cervical Cancer
Sarcoma Cancer
• Combination studies with pipeline assets ongoing or planned by both Incyte and MacroGenics
20 October 2019MGD013
MGD013: First Bispecific Checkpoint Molecule in Clinical Trials
• Simultaneous and/or independent blockade of two
Function/
MoA checkpoint molecules
LAG-3 LAG-3
• Reactivation of exhausted T cells
• Ph. 1 dose expansion in nine tumor types (solid and
PD-1 PD-1
Clinical liquid); checkpoint-naïve and checkpoint-experienced
Studies • Phase 2/3 MAHOGANY study with margetuximab and
chemotherapy in gastric cancer (Module B) planned
• >100 patients enrolled in ongoing Ph. 1 dose
Status expansion; clinical update expected 2H19
• Exploring correlative biomarkers (with Nanostring)
MacroGenics’
Retained • Global rights (excl. Greater China)
Rights
21 October 2019MGD013
MGD013: Synergistic T-cell Activation
DART construct enhances T-cell activation vs. anti-PD-1 + anti-LAG-3 mAbs in vitro
Enhancement of Primary T-cell Response Following SEB Stimulation
MGD013 (PD-1
MGD013 x LAG-3
(PD-1 DART
x LAG-3 mol.)
DART)
MGA012 + MG Anti-LAG-3 + NS
PD-1 × LAG-3
DART Molecule
PD-1 LAG-3
Nivo* + 25F7*
MGA012 Anti-PD-1
25 nM
Nivo* Anti-PD-1 6.25 nM
1.56 nM
MG's Anti-LAG-3 0.39 nM
0.09 nM
Ratio-paired t-test (25 nM group):
BMS' Anti-LAG-3 (25F7* ) 0.024 nM *p = 0.0262
0.006 nM **p = 0.0022
NS = not significant
Control IgG Number of subjects = 11–13
0 50 100 150 200 250 300 350 400 450
Relative IFN-γ Induction (% of 25 nM MGA012, mean ± sem)
*IFNγ release by 25 nM MGA012 = 3276±744 pg/ml.
22 October 2019MGD013
Rationale for MGD013 in MAHOGANY Phase 2/3 Study: High LAG-3 Expression
• LAG-3 positivity:
88% (30/34) observed
across gastric cancer
samples*
H&E and LAG-3 IHC profile for
gastric cancer patient sample 20x H&E LAG-3 IHC Isotype Control
• cPR in 67 y.o. gastric cancer patient in MGD013 monotherapy Phase 1 study
− Refractory to nivolumab
− Complete resolution of target lesions
− Treatment ongoing as of May 2019 for ~31 weeks
* IHC performed using anti-LAG-3 mAb EPR43292(2); Positivity defined as detection of at least one LAG-3 positive Tumor Infiltrating Lymphocyte (TIL)
23 October 2019Enoblituzumab
Enoblituzumab: Potential Leading Anti-B7-H3 mAb
Leveraging immune modulation through Fc optimization
• Fc region optimized to enhance immune response,
Function/ including ADCC
MoA
• Evidence of T-cell immunomodulation
B7-H3 B7-H3
• Ph. 1 study in SCCHN and NSCLC (including PD-L1
Fab
Region
Clinical negative)
Studies • Ph. 2/3 study in SCCHN in combination with MGA012
(anticipated start 4Q19)
Fc Region Status • Ph 1. data in SCCHN and NSCLC reported at SITC 2018
MacroGenics’
Retained • Global rights (excl. Greater China)
Rights
24 October 2019Enoblituzumab
Rationale for Targeting B7-H3 in Cancer
Associated with adverse clinical features and outcome in various solid tumors
Tumor Cells
Expression on:
• Primary tumor & metastases
• Cancer stem cells
• Tumor stroma and vasculature
Myeloid-Derived
Suppressor Cells
Cancer Potential immunological role
Stem Cells • Inhibition of T-cell activation
• Correlated with lack of response to anti-
PD-1 therapy(a)
Tumor-autonomous role
• Migration & invasion
• Tumor metabolic advantage
• Associated with chemotherapy resistance
Tumor Vasculature T Cells
(a) Yonesaka, et al., CCR, 2018
25 October 2019Enoblituzumab
Confirmed High Penetrance in Broad Set of Solid Tumors
Majority of B7-H3 positive tumors express high levels of B7-H3 (≥ 2+)
IHC Summary of >1 ,400 Tumor Tissue Samples Screened
Potential Indications B7-H3 Positive(a) 2+ or Above
Head and Neck 19/19 100% 19/19 100%
Kidney Cancer 77/78 99% 75/78 96%
Glioblastoma 65/66 98% 63/66 95%
Thyroid Cancer 34/35 97% 33/35 94%
Enoblituzumab
+Anti-PD-1 Mesothelioma 41/44 93% 39/44 89%
Combination Melanoma 132/146 90% 94/146 64%
Study Indications
Prostate Cancer 88/99 89% 51/99 52%
Evaluated
Pancreas Cancer 69/78 88% 45/78 58%
Bladder 134/156 86% 123/156 79%
Lung Cancer 324/379 85% 300/379 79%
Breast Cancer 189/249 76% 156/249 63%
Ovarian Cancer 59/79 75% 36/79 46%
Limited expression in normal tissue favorable profile for targeting B7-H3
(a) B7-H3 positivity reflects any grade staining via fixed tumor microarray; B7-H3 is expressed on tumor as well as tumor vasculature.
26 October 2019Enoblituzumab
Antitumor Activity in SCCHN Patients (Anti-PD-1/PD-L1 Naïve) + anti-PD-1 mAb
Induction of tumor regression in SCCHN patients, irrespective of HPV status
HPV-
60 HPV+
First new lesion
Change from Baseline (%)
40
Treatment ongoing
20
0
HPV- -20
50 HPV+ -40
40
* Treatment ongoing -60
30 -80
20 -100
0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 100 105 110 115 120
10 Weeks Since Treatment Indication
0
-10 *
-20
-30
-40
-50
All Patients B7-H3 (Tumor) ≥ 10%
-60 *
-70 N= 18 15
-80 CR+PR 6/18 (33.3%) 6/15 (40.0%)
-90 *
CR+PR+SD 11/18 (61.1%) 11/15 (73.3%)
-100
*
Data cut-off date: October 12, 2018. Received ≥1 prior line of chemotherapy and TKI treatment. B7-H3 testing was retrospective. (Presented SITC 2018)
27 October 2019Enoblituzumab
Antitumor Activity in NSCLC Patients (Anti-PD-1/PD-L1 Naїve) + anti-PD-1 mAb
Induction of tumor regression in NSCLC patients withEnoblituzumab
Encouraging Enoblituzumab + Anti-PD-1 Combo Data
SCCHN and NSCLC benchmarks
SCCHN Study Results
Agent Enoblituzumab Nivolumab Pembrolizumab Pembrolizumab
(Study) + Pembrolizumab (CM-141)(a) (KN-012)(b) (KN-040)(c)
N 18 240 174 247
ORR 33.3% 13% 16% 15%
NSCLC Study Results
Agent Enoblituzumab Nivolumab Nivolumab Pembrolizumab
(Study) + Pembrolizumab (CM-057)(d) (CM-017)(e) (KN-001)(f)
Histology Both Non-Squamous Squamous Both
PD-L1 Status PD-L1Enoblituzumab
Enoblituzumab Phase 2/3 Study: Registration Path in 1st Line SCCHN
Planned initiation of global study in 4Q2019
Phase 2 Phase 3
(n=50 per arm)
Control Arm:
1L pembrolizumab+ chemo (n=260 per arm)
Squamous
Cell Experimental Arm #1: Control Arm:
enoblituzumab + MGA012 Pembrolizumab + chemo Primary
Carcinoma
R R BLA
Go/
Endpoint:
of the Head Experimental Arm #2:
No-Go
Experimental Arm: OS
and Neck enoblituzumab + MGA012+ chemo Enoblituzumab* + MGA012 ± chemo
(SCCHN) Assess
Patients Experimental Arm #3: Safety/efficacy of
Experimental
MGA012 + chemo
Arms #1 and #2
* Pending chronic tox study.
30 October 2019Flotetuzumab
Flotetuzumab: CD123 × CD3 DART Molecule
• Redirected T-cell killing against leukemia cells
Function/ – Eliminates leukemic stem cells
MoA – Spares normal hematopoietic stem cells
– Engages any T-cell without HLA-restriction
• Ph.1 monotherapy study in relapsed or refractory acute
CD123 CD3
Clinical myeloid leukemia (r/r AML)
Studies • Ph.1 combination study with MGA012 in r/r AML
(initiated 3Q19 ex-US)
• Preliminary Ph.1 monotherapy data at ASH 2018
• Updated Ph.1 monotherapy data expected 2H19
Status
– 50 Patients enrolled at recommended Phase 2 dose,
including 30 patients with primary refractory AML
MacroGenics’
Retained • Global rights
Rights
31 October 2019Flotetuzumab
Flotetuzumab: Phase 1/2 Monotherapy Study Design
Dose Escalation Dose Expansion #1 Dose Expansion #2
Intra-patient and multi-patient Data presented at ASH 2018 Enrollment completed;
escalation cohorts Present data in 2019
Establish Target Dose
and Schedule (n=47)
Relapsed/Refractory AML (n=31)
Target Dose: 500 ng/kg/day
Cycle 1: Continuous Infusion over 28 Days Relapsed/Refractory AML (n=25)
Cycle ≥ 2: 4 Days On/ 3 Days Off Incorporated multi-step, lead-in dosing Enrich for primary refractory sub-pop.
and supportive care to mitigate CRS
Further optimize lead-in dosing;
evaluate correlative biomarkers
• Primary refractory population:
‒ Refractory to ≥2 induction attempts, or
‒ 1st relapse with initial CR duration of 6 months)
• No prior allogeneic hematopoietic cell transplant
• Safety and disease status assessed by modified IWG criteria
Endpoints
• Gene expression profiling performed using NanoString® PanCancerIO 360™ assay
32 October 2019Flotetuzumab
Primary Refractory AML Patients Have Been Most Responsive to Flotetuzumab
Monotherapy dose expansion #1 data presented at ASH 2018
50 Primary Refractory
Bone Marrow Blast Change from Baseline (%)
40
Relapsed Median Duration of
30 Response = 3.1 mos.
Failed 2 Cycles of HMA
20
10
SD SD SD SD SD SD SD SD SD SD SD PR(b) MLF CR CR CR CRi CRi(a)
0
-10 PD PD PD PD PD PD PD
-20
-30
-40
-50 Benchmark
AML Population ORR CR/CRi CR/CRi
-60
-70 Primary Refractory 6/17 (35.3%) 5/17 (29.4%) 13%(c)
-80
-90 Relapse 1/7 (14.3%) 0/7 (0%) —
-100
• 31 Patients treated at RP2D: 27 response evaluable (2 PD on PB blasts), 25 pts in waterfall plot
• 3 Patients non-evaluable pts (2 pts withdrew consent, 1 pt. withdrawn due to TRAE); 1 pt. ongoing
• Acceptable safety: primarily low-grade CRS, w/Grade 3=12.9% (4/31 patients)
Data cut-off date: Nov. 1, 2018
CR=Complete Response; CRi=Complete Response with incomplete hematological improvement; MLF=Morphologic Leukemia-free state; PR=Partial Response; SD=Stable Disease; PD=Treatment Failure
(a) Patient subsequently underwent HSCT in remission
(b) Patient with PR had duration of response = 1.4 months
(c) CR/CRp rate reported by Kantarjian, et al. (Cancer 2018) in large-scale analysis of chemotherapy-based salvage therapy in primary refractory AML patients (Presented ASH 2018)
33 October 2019Financial Overview
• $272M Cash, cash equivalents and marketable securities as of June 30, 2019
• Historical financial details:
6 Mos. Ended June 30,
$ in Millions 2014 2015 2016 2017 2018 2019 2018
Total Revenues $48 $101 $92 $158 $60 $20 $24
R&D Expense 70 98 122 147 191 99 98
Total Operating Expenses 86 121 152 180 231 121 118
Cash & Investments 158 339 285 305 233 272 301
• Revenues from collaborative and government agreements (>$450M since 2013 IPO):
$150
$ in Millions
$100
$50
$0
2014 2015 2016 2017 2018
34 October 2019Anticipated Development Progress of Core Product Candidates in 2019
Margetuximab Enoblituzumab
(Anti-HER2 mAb) (Anti-B7-H3 mAb)
Positive SOPHIA study PFS data Initiate MGA012 combo study (4Q)
Updated gastric combo data
Initiated MAHOGANY study
SOPHIA interim OS (n=270) (4Q)
BLA submission (4Q)
MGA012(a) MGD013 Flotetuzumab
(Anti-PD-1 mAb) (PD-1 × LAG-3 DART molecule) (CD123 × CD3 DART molecule)
(Subject to Incyte’s disclosure) Present clinical update (4Q) Initiated MGA012 combo study
Present additional mono. data (4Q)
(a) MacroGenics retains rights to develop its pipeline assets in combination with MGA012 and to manufacture a portion of global clinical and commercial supply needs of MGA012.
35 October 2019Thank You!
Investor Relations Inquiries:
Jim Karrels – Senior Vice President, CFO
301-354-2681 | karrelsj@macrogenics.com
Anna Krassowska, Ph.D. – Vice President,
Investor Relations and Corporate Communications
301-461-4042 | krassowskaa@macrogenics.com
Business Development Inquiries:
Eric Risser – Senior Vice President, Chief Business Officer
301-354-2640 | rissere@macrogenics.com
www.macrogenics.com
Link to our latest presentations:
http://ir.macrogenics.com/events.cfm
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