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June 2020
Pioneering the Next Generation ofRedirected T Cell Engaging Therapeutics in Immuno-Oncology
2
Agenda
• The Landscape: Breakthroughs in Cancer Immunotherapy
• Corporate Overview: Leader in T Cell Engaging Therapy in Solid Tumors
• The Opportunity: T Cell Engaging Therapy in Solid Tumors – Game Changing
• The Maverick Solution: COBRA™ Therapeutic Platform
• COBRATM Platform Validation: Lead Candidate MVC-101
• Path to Treating Patients: Clinical Development Strategy
• Single Focus on Developing T Cell Engaging Therapies: COBRA™ Pipeline
3
IL-2 approved for metastatic
renal cell carcinoma
PROLEUKIN® (aldesleukin)
Breakthroughs in Cancer Immunotherapy Development
20182015
First CAR-T Cell Therapy approved for ALL
KYMRIAH® (tisagenlecleucel)
James Allison, PhD & TasukuHonjo, MD, PhD win Nobel Peace
Prize for Checkpoint Inhibitors
2014
First Check Point Inhibitors (Anti-PD-1) approved for
advanced melanomaKEYTRUDA® (pembrolizumab),
OPDIVO® (nivolumab)
ALL = acute lymphoblastic leukemia
First Bispecific T Cell Engager approved for Precursor B cell ALL
BLINCYTO® (blinatumomab) CD19 x CD3
First Oncolytic Virus approved for melanoma
IMLYGIC® (T-VEC)
FDA
FDA
FDA
First autologous cellular immunotherapy approved
for prostate cancerPROVENGE® (sipuleucel-T)
1992
2010
2011
2017
First Checkpoint Inhibitor (Anti-CTLA-4) approved
for metastatic melanomaYERVOY® (ipilimumab)
First report of efficacy & safety of CAR-T cell
Therapy or a Bispecific T Cell Engager
in solid tumors
FDA
FDA
FDA
FDA= accelerated approval www.drugs.com/approvalhistory
www.nobelprize.org/prizes/medicine/2018/press-release
CAR-T Cell Therapy approved for B cell lymphoma
YESCARTA® (axicabtagene ciloleucel)
FDA
202X
FDA
mavericktx.com
CORPORATE OVERVIEW
5
Maverick Therapeutics Introduction
• Immuno-Oncology company launched in 2017
• Our Mission: Become the Leader in T Cell Engaging Therapy in Solid Tumors
COBRA™: A novel conditionally active T cell engager designed to safely target solid tumors with highly
specific and potent activity
6
Partnerships
Focus
Strategic Validation
$125M of Committed Funding
Validation of approach, scientific platform and programs by key industry leaders
Develop proprietary, best-in-class, T cell-engaging antibody therapeutics
5 year drug development project based on the promise
of early-stage research
7
Leadership Team
8
COBRA™ Platform Pipeline
ExpectedQ1 2021
ExpectedH2 2021
9
I/O Landscape: Enormous Unmet Need in Solid Tumors
Hematological Cancers Solid Tumor Cancers
Cancer Types Lymphoma, leukemia, myelomaBreast, lung, prostate, colorectal, melanoma, uterine & ovarian, kidney & renal, head & neck, pancreas, others
Therapies
• Bispecific T cell engagers- Blincyto® (blinatumomab)
• CAR-T - Kymriah® (tisagenlecleucel)- Yescarta® (axicabtagene
ciloleucel)
• Checkpoint Inhibitors - Opdivo® (nivolumab)- Keytruda® (pembrolizumab)- Yervoy® (ipilimumab)
Average Overall Response Rates
40 – 93%** 0.5 – 24%**
# of new cases* 174,000 = ~10% of all cancers 1,561,000 = ~90% of all cancers
* American Cancer Society, 2019** Based on efficacy data in prescribing information for each therapy listed
There are 900% as many solid tumor cancers as there are hematological cancers
mavericktx.com
T Cell Therapy in Solid Tumors = Game Changing Opportunity
THE OPPORTUNITY
11
The Promise of T Cell Engagers
• T cell engagers significantly enhance immune response to tumors relative to antibody dependent cellular cytotoxicity (ADCC)
blinatumomab
rituximab100,000 fold
Dreier, et al. Int. J. Cancer, 2002Sp
ecifi
c Cyt
otox
icity
[%]
Antibody Concentration [ng/ml]
• T cell engagers are a class of bispecific antibodies (bsAbs) used for cancer treatment
• They are a fusion between tumor-targeting and T cell engaging recombinant antibody fragments
12
B-cell counts of 20 patients treated with
blinatumomab
Klinger, et al. Blood, 2012
T cell engagers designed to treat B cell malignancies are tolerated, even though they transiently deplete normal B cells in patients
The Challenge of T Cell Engagers Beyond Hematological Cancers
T cell engagers bind cell surface targets regardless of whether expressed on the tumor or on healthy tissues
Healthy Tissue Tumor Tissue
T cell
For solid tumor targets, damage to healthy tissues by T cell engagers can result in significant toxicity & limits patient response by lowering the dose that can be safely administered
T cell engagers are more sensitive than IHC. Targets thought to be expressed uniquely on tumor, but not on healthy tissue, often still elicit a T cell response due to low-level expression
mavericktx.com
COBRA™: A Novel Conditionally Active Bispecific Antibody
THE MAVERICK SOLUTION
14
Protease Activity Is Upregulated in Tumorsbut Not in Healthy Tissues
Protease Activity is Highly Regulatedin Healthy Tissue
1. Transcription
2. TranslationSecretionLocalization
Zymogen Active Protease
4. Inhibition
Protease + Inhibitor Complex
3. Activation
Increased Protease Activity in the Tumor Microenvironment
Adapted from Winer, et al. Mol Cancer Ther 2018
The COBRA™ platform takes advantage of the tumor’s unique proteolytic microenvironment for T cell activation
15
COBRA™ = Conditional Bispecific Redirected ActivationαEGFR sdAb inactive VLαCD3 VH αEGFR sdAb inactive VHαCD3 VL αHSA sdAb
Protease Cleavable Linker8 a.a. 8 a.a.
COBRA™ Construct Design and Predicted Folding
Inactivated VH & VL domains pair with αCD3 VH & VL domains
min2.5 5 7.5 10 12.5 15 17.5 20 22.5
mAU
0
100
200
300
400
500
600
700
DAD1 A, Sig=280,2 Ref=off (JK180703 SEC lot 803 2018-07-03 11-14-55\005-P1-A5-Pro186 lot PL-0803.D)
14.
698
17.
004
15.
741
Monomer = 97.5%
Analytical Size Exclusion Chromatography
Predicted COBRA™ Folding
EGFR/MMP9 = MVC-101 = Maverick COBRA™ Program 1
Protein A and Preparative SEC purification
16
MVC-101 Active Dimer
αCD3 agonist (dimer of αCD3 VH and VL )
Binds EGFRBinds CD3
MVC-101 Cleavage Products
αCD3 VH and VL
inactive VH and VL
Binds EGFRImpaired CD3 binding Binds serum albumin
+
MVC-101
Cleaved MVC-101 Dimerizes to Form the Active Molecule
Binds EGFRImpaired CD3 bindingBinds serum albumin
17
COBRAs Are Predictive From Pre-Clinical to Clinical by Design
sdAb(monovalent EGFR binding)
MVC-101(bivalent EGFR binding)
Active MVC-101(tetravalent EGFR binding)
αEGFR KD (nM)
αEGFRKD (nM)
αCD3 KD (nM)
αHSAKD (nM)
αEGFRKD (nM)
αCD3 KD (nM)
Human 2.7 0.12 nb 11.3 <0.01 1.7
Cyno 6.3 0.14 nb 10.8 <0.01 2.4
Mouse nb* nb nb 106.3 nb nb*nb = no binding
• Binding kinetics to EGFR, serum albumin and CD3ε were assessed via the Octet system
Note: MVC-280 binds murine B7H3
18
COBRA™ Mechanism of AcKon Video
https://www.mavericktx.com/technology/#our-scienceVideo available at:
mavericktx.com
MVC-101: MOA Validating Data
COBRA™ PLATFORM VALIDATION
20
Activated MVC-101 Demonstrates Potent In Vitro Activity
HT29 Tumor CellsE:T 10:148 hours
0.0010.01 0.1 1 10
1001000
0.0
0.5
1.0
T cell Killing Assay
Concentration (pM)
Tum
or c
ells
- RL
U
MVC-NCLMVC-101MVC-101 Pre-Cleaved
200X(Non-cleavable)
21
0 5 10 15 20 25 30 35 40 450
500
1000
1500
2000
SCC25
Days post initial dose0 5 10 15 20 25 30 35
0
500
1000
1500
2000
LoVo
Days post initial dose
Tum
or V
olum
e (m
m3 )
MVC-NCL - 100 µg/kgMVC-101 - 100 µg/kgMVC-101 - 20 µg/kgMVC-101 - 4 µg/kg
0 5 10 15 20 25 30 350
500
1000
1500
2000
HT29
Days post initial dose
MVC-101 Regresses Established Solid Tumors in Mice
Dosed every 3 days for 7 doses total
Cell Lines:
8,774 EGFR/cell 33,218 EGFR/cell 239,344 EGFR/cell
22
0 24 48 72 96 120 144 1680.1
1
10
100
1000
10000
Time (Hours)
Pla
sma
Conc
(ng/
mL)
Pre-Cleaved MVC-101 - 100 µg/kgMVC-101 - 100 µg/kgMVC-NCL - 100 µg/kg
PK in non-tumor bearing mice
Cleaved MVC-101 Clears More Rapidly Than Intact MVC-101
MVC-101
MVC-NCL (Non-cleavable)
MVC-101Pre-Cleaved
0 5 10 15 20 25 30 350
500
1000
1500
2000
LoVo
Days post dose initiation
Tum
or V
olum
e (m
m3 )
MVC-NCL - 100 µg/kgMVC-101 - 100 µg/kgPre-Cleaved MVC-101 - 100 µg/kg
23
Biol
ogic
al R
espo
nse
Leve
l
Log (exposure)
Preclinical Results Predict Increased Therapeutic WindowMVC-101 exposures at efficacious doses relative to tolerated doses predict an increased therapeutic window compared to inherently active T cell engagers
Inherently Active T Cell Engagers COBRA™ MVC-101
Log (exposure)
IncreasedTherapeutic
Window
30 - 100x
Validated by two gold standard methodologies in pre-clinical models for MVC-101 and MVC-280
Efficacious Dose
Maximum Tolerated
DoseBi
olog
ical
Res
pons
e Le
vel
24
Clinical Development Strategy
PATH TO TREATING PATIENTS
25
FDA’s recommended
starting dose
Biol
ogic
al R
espo
nse
Leve
l
Log (exposure)
COBRA™ Safety Mechanisms Enable Higher Star;ng Dose• Regulatory interaction reveals different philosophies
o FDA: Starting dose calculated based on safety aloneo Ex-US: Starting dose calculated based on safety and predicted efficacy
• COBRA safety features & robust pre-clinical safety package combined with an ex-US strategy allow Maverick to start at a higher dose
COBRA™ MVC-101
Ex-US recommended
startin
g dose
26
• Begin US IND filing once sufficient safety data has been collected
• Run Expansion phase in Australia & US across 3-4 solid tumor indications
Phase 1: Dose Escalabon Phase 2: Dose Expansion
• Uflize ex-US Regulatory feedback to accelerate fme to potenfal signs of efficacy with higher starfng dose
Australia Australia & US
*Note: Starting dose recommendation and dose fold increases are estimates based on Regulatory feedback
Dose Level A
Dose Level B
Dose Level C
Cohort Dose Dose Level D
Dose Level E
Dose Level F
Dose Level G
Dose Level H
Dose Level I
Dose Level J
Dose Level K
Dose Level L
Solid Tumor Type 3N = 16-20
Solid Tumor Type 2N = 16-20
Solid Tumor Type 1N = 16-20
FDA Ex-US
Dose Level F
Dose Level G
Dose Level H
Dose Level I
Dose Level J
Dose Level K
Dose Level L
Incr
easin
g Do
se*
Projected Ph 2 Dose
Star]ng Dose Recommenda]on*
Sub-therapeutic Dose
TherapeuGc Dose Range
Clinical Development: Speed to Proof of Concept
27
EGFR Is Expressed on a Wide Range of Solid Tumors
Head and Neck Squamous Cell
Carcinoma (HNSCC)Colorectal Cancer (CRC) Non-Small Cell Lung
Cancer (NSCLC)
EGFR Expression Levels
Constitutively high in all subtypes1
High in KRAS mutant and wildtype2
High and consistent in EGFR mutant3
Line of Therapy• ≥ 3rd line• Potential 2nd line with
PD-1 entering 1st line
Currently very limited options in ≥ 3rd line KRAS mutant (50-60%) and wildtype
• Limited treatment options after EGFR-mutant TKI failures
• PD-1 not a factor
Standard of Care Objective Response Rate
Keytruda® (pembrolizumab)4
16%
Stivarga®(regorafenib)5
1%
Taxotere®(docetaxel)6
15%
1. Zimmerman M, et al. (2006), Radiat Oncol, 10.1186/1748-717X-1-112. Callisia C, et al. (2015), Journal of Gastrointestinal Oncol, 6(6):660-6673. Mascaux C, et al. (2011), Clin Cancer Res, 24:7796-8074. https://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf5. http://labeling.bayerhealthcare.com/html/products/pi/Stivarga_PI.pdf6. https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020449s071lbl.pdf
• EGFR-expressing solid tumors include but are not limited to colorectal, head & neck, renal, pancreaYc, cervical and non-small cell lung cancers
28
COBRA™ Pipeline
SINGLE FOCUS ON DEVELOPING T CELL ENGAGING THERAPIES
29
COBRA™ Platform Pipeline
ExpectedQ1 2021
ExpectedH2 2021
30
Maverick Achievements and Outlook
ü Designed a condifonally acfve, highly potent T cell engaging plajorm focused exclusively on solid tumor applicafon, called COBRA
ü Demonstrated protease mediated-linker cleavage increases COBRA directed T cell killing potency by up to 200-fold in vitro
ü Demonstrated COBRA-mediated regressions of established solid tumors in xenograk-bearing mice in mulfple in vivo models
ü Validated that COBRA acfvity is dependent on tumor microenvironment mediated COBRA acfvafon
ü Established the circulafng half-life of lead candidate MVC-101 allows for a weekly dosing regimen
ü Demonstrated built-in safety design; once proteolyfcally acfvated, MVC-101 is more rapidly cleared from the peripheral blood
ü Efficacy and exploratory safety studies validate the COBRA mechanism of acfon and establish a 30-100x increase in the therapeufc window relafve to standard inherently acfve T cell engagers
ü Established next generafon dual targefng in vitro proof of concept
ü First-in-class programs with best-in-class design
Ø Presentation of MVC-280 data at several conferences
Ø COBRA publication in high impact journal
Ø Disclosure of additional COBRA pipeline lead candidates
Ø Initiate MVC-101 Phase 1/2 Dose Escalation (Q1)
Ø Initiate MVC-280 Phase 1/2 Dose Escalation (H2)
Ø Demonstrate next generation COBRA efficacy in vivo
Achievements Outlook
2020
2021
31
Thank You