pioneering the next generation of redirected t cell ......renal cell carcinoma proleukin®...
TRANSCRIPT
![Page 1: Pioneering the Next Generation of Redirected T Cell ......renal cell carcinoma PROLEUKIN® (aldesleukin) Breakthroughs in Cancer Immunotherapy Development 2015 2018 First CAR-T Cell](https://reader033.vdocuments.mx/reader033/viewer/2022060506/5f1f3559558e493ca7252aa6/html5/thumbnails/1.jpg)
1
June 2020
Pioneering the Next Generation ofRedirected T Cell Engaging Therapeutics in Immuno-Oncology
![Page 2: Pioneering the Next Generation of Redirected T Cell ......renal cell carcinoma PROLEUKIN® (aldesleukin) Breakthroughs in Cancer Immunotherapy Development 2015 2018 First CAR-T Cell](https://reader033.vdocuments.mx/reader033/viewer/2022060506/5f1f3559558e493ca7252aa6/html5/thumbnails/2.jpg)
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
![Page 3: Pioneering the Next Generation of Redirected T Cell ......renal cell carcinoma PROLEUKIN® (aldesleukin) Breakthroughs in Cancer Immunotherapy Development 2015 2018 First CAR-T Cell](https://reader033.vdocuments.mx/reader033/viewer/2022060506/5f1f3559558e493ca7252aa6/html5/thumbnails/3.jpg)
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
![Page 4: Pioneering the Next Generation of Redirected T Cell ......renal cell carcinoma PROLEUKIN® (aldesleukin) Breakthroughs in Cancer Immunotherapy Development 2015 2018 First CAR-T Cell](https://reader033.vdocuments.mx/reader033/viewer/2022060506/5f1f3559558e493ca7252aa6/html5/thumbnails/4.jpg)
mavericktx.com
CORPORATE OVERVIEW
![Page 5: Pioneering the Next Generation of Redirected T Cell ......renal cell carcinoma PROLEUKIN® (aldesleukin) Breakthroughs in Cancer Immunotherapy Development 2015 2018 First CAR-T Cell](https://reader033.vdocuments.mx/reader033/viewer/2022060506/5f1f3559558e493ca7252aa6/html5/thumbnails/5.jpg)
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
![Page 6: Pioneering the Next Generation of Redirected T Cell ......renal cell carcinoma PROLEUKIN® (aldesleukin) Breakthroughs in Cancer Immunotherapy Development 2015 2018 First CAR-T Cell](https://reader033.vdocuments.mx/reader033/viewer/2022060506/5f1f3559558e493ca7252aa6/html5/thumbnails/6.jpg)
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
![Page 7: Pioneering the Next Generation of Redirected T Cell ......renal cell carcinoma PROLEUKIN® (aldesleukin) Breakthroughs in Cancer Immunotherapy Development 2015 2018 First CAR-T Cell](https://reader033.vdocuments.mx/reader033/viewer/2022060506/5f1f3559558e493ca7252aa6/html5/thumbnails/7.jpg)
7
Leadership Team
![Page 8: Pioneering the Next Generation of Redirected T Cell ......renal cell carcinoma PROLEUKIN® (aldesleukin) Breakthroughs in Cancer Immunotherapy Development 2015 2018 First CAR-T Cell](https://reader033.vdocuments.mx/reader033/viewer/2022060506/5f1f3559558e493ca7252aa6/html5/thumbnails/8.jpg)
8
COBRA™ Platform Pipeline
ExpectedQ1 2021
ExpectedH2 2021
![Page 9: Pioneering the Next Generation of Redirected T Cell ......renal cell carcinoma PROLEUKIN® (aldesleukin) Breakthroughs in Cancer Immunotherapy Development 2015 2018 First CAR-T Cell](https://reader033.vdocuments.mx/reader033/viewer/2022060506/5f1f3559558e493ca7252aa6/html5/thumbnails/9.jpg)
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
![Page 10: Pioneering the Next Generation of Redirected T Cell ......renal cell carcinoma PROLEUKIN® (aldesleukin) Breakthroughs in Cancer Immunotherapy Development 2015 2018 First CAR-T Cell](https://reader033.vdocuments.mx/reader033/viewer/2022060506/5f1f3559558e493ca7252aa6/html5/thumbnails/10.jpg)
mavericktx.com
T Cell Therapy in Solid Tumors = Game Changing Opportunity
THE OPPORTUNITY
![Page 11: Pioneering the Next Generation of Redirected T Cell ......renal cell carcinoma PROLEUKIN® (aldesleukin) Breakthroughs in Cancer Immunotherapy Development 2015 2018 First CAR-T Cell](https://reader033.vdocuments.mx/reader033/viewer/2022060506/5f1f3559558e493ca7252aa6/html5/thumbnails/11.jpg)
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
![Page 12: Pioneering the Next Generation of Redirected T Cell ......renal cell carcinoma PROLEUKIN® (aldesleukin) Breakthroughs in Cancer Immunotherapy Development 2015 2018 First CAR-T Cell](https://reader033.vdocuments.mx/reader033/viewer/2022060506/5f1f3559558e493ca7252aa6/html5/thumbnails/12.jpg)
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
![Page 13: Pioneering the Next Generation of Redirected T Cell ......renal cell carcinoma PROLEUKIN® (aldesleukin) Breakthroughs in Cancer Immunotherapy Development 2015 2018 First CAR-T Cell](https://reader033.vdocuments.mx/reader033/viewer/2022060506/5f1f3559558e493ca7252aa6/html5/thumbnails/13.jpg)
mavericktx.com
COBRA™: A Novel Conditionally Active Bispecific Antibody
THE MAVERICK SOLUTION
![Page 14: Pioneering the Next Generation of Redirected T Cell ......renal cell carcinoma PROLEUKIN® (aldesleukin) Breakthroughs in Cancer Immunotherapy Development 2015 2018 First CAR-T Cell](https://reader033.vdocuments.mx/reader033/viewer/2022060506/5f1f3559558e493ca7252aa6/html5/thumbnails/14.jpg)
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
![Page 15: Pioneering the Next Generation of Redirected T Cell ......renal cell carcinoma PROLEUKIN® (aldesleukin) Breakthroughs in Cancer Immunotherapy Development 2015 2018 First CAR-T Cell](https://reader033.vdocuments.mx/reader033/viewer/2022060506/5f1f3559558e493ca7252aa6/html5/thumbnails/15.jpg)
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
![Page 16: Pioneering the Next Generation of Redirected T Cell ......renal cell carcinoma PROLEUKIN® (aldesleukin) Breakthroughs in Cancer Immunotherapy Development 2015 2018 First CAR-T Cell](https://reader033.vdocuments.mx/reader033/viewer/2022060506/5f1f3559558e493ca7252aa6/html5/thumbnails/16.jpg)
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
![Page 17: Pioneering the Next Generation of Redirected T Cell ......renal cell carcinoma PROLEUKIN® (aldesleukin) Breakthroughs in Cancer Immunotherapy Development 2015 2018 First CAR-T Cell](https://reader033.vdocuments.mx/reader033/viewer/2022060506/5f1f3559558e493ca7252aa6/html5/thumbnails/17.jpg)
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
![Page 18: Pioneering the Next Generation of Redirected T Cell ......renal cell carcinoma PROLEUKIN® (aldesleukin) Breakthroughs in Cancer Immunotherapy Development 2015 2018 First CAR-T Cell](https://reader033.vdocuments.mx/reader033/viewer/2022060506/5f1f3559558e493ca7252aa6/html5/thumbnails/18.jpg)
18
COBRA™ Mechanism of AcKon Video
https://www.mavericktx.com/technology/#our-scienceVideo available at:
![Page 19: Pioneering the Next Generation of Redirected T Cell ......renal cell carcinoma PROLEUKIN® (aldesleukin) Breakthroughs in Cancer Immunotherapy Development 2015 2018 First CAR-T Cell](https://reader033.vdocuments.mx/reader033/viewer/2022060506/5f1f3559558e493ca7252aa6/html5/thumbnails/19.jpg)
mavericktx.com
MVC-101: MOA Validating Data
COBRA™ PLATFORM VALIDATION
![Page 20: Pioneering the Next Generation of Redirected T Cell ......renal cell carcinoma PROLEUKIN® (aldesleukin) Breakthroughs in Cancer Immunotherapy Development 2015 2018 First CAR-T Cell](https://reader033.vdocuments.mx/reader033/viewer/2022060506/5f1f3559558e493ca7252aa6/html5/thumbnails/20.jpg)
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)
![Page 21: Pioneering the Next Generation of Redirected T Cell ......renal cell carcinoma PROLEUKIN® (aldesleukin) Breakthroughs in Cancer Immunotherapy Development 2015 2018 First CAR-T Cell](https://reader033.vdocuments.mx/reader033/viewer/2022060506/5f1f3559558e493ca7252aa6/html5/thumbnails/21.jpg)
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
![Page 22: Pioneering the Next Generation of Redirected T Cell ......renal cell carcinoma PROLEUKIN® (aldesleukin) Breakthroughs in Cancer Immunotherapy Development 2015 2018 First CAR-T Cell](https://reader033.vdocuments.mx/reader033/viewer/2022060506/5f1f3559558e493ca7252aa6/html5/thumbnails/22.jpg)
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
![Page 23: Pioneering the Next Generation of Redirected T Cell ......renal cell carcinoma PROLEUKIN® (aldesleukin) Breakthroughs in Cancer Immunotherapy Development 2015 2018 First CAR-T Cell](https://reader033.vdocuments.mx/reader033/viewer/2022060506/5f1f3559558e493ca7252aa6/html5/thumbnails/23.jpg)
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
![Page 24: Pioneering the Next Generation of Redirected T Cell ......renal cell carcinoma PROLEUKIN® (aldesleukin) Breakthroughs in Cancer Immunotherapy Development 2015 2018 First CAR-T Cell](https://reader033.vdocuments.mx/reader033/viewer/2022060506/5f1f3559558e493ca7252aa6/html5/thumbnails/24.jpg)
24
Clinical Development Strategy
PATH TO TREATING PATIENTS
![Page 25: Pioneering the Next Generation of Redirected T Cell ......renal cell carcinoma PROLEUKIN® (aldesleukin) Breakthroughs in Cancer Immunotherapy Development 2015 2018 First CAR-T Cell](https://reader033.vdocuments.mx/reader033/viewer/2022060506/5f1f3559558e493ca7252aa6/html5/thumbnails/25.jpg)
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
![Page 26: Pioneering the Next Generation of Redirected T Cell ......renal cell carcinoma PROLEUKIN® (aldesleukin) Breakthroughs in Cancer Immunotherapy Development 2015 2018 First CAR-T Cell](https://reader033.vdocuments.mx/reader033/viewer/2022060506/5f1f3559558e493ca7252aa6/html5/thumbnails/26.jpg)
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
![Page 27: Pioneering the Next Generation of Redirected T Cell ......renal cell carcinoma PROLEUKIN® (aldesleukin) Breakthroughs in Cancer Immunotherapy Development 2015 2018 First CAR-T Cell](https://reader033.vdocuments.mx/reader033/viewer/2022060506/5f1f3559558e493ca7252aa6/html5/thumbnails/27.jpg)
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
![Page 28: Pioneering the Next Generation of Redirected T Cell ......renal cell carcinoma PROLEUKIN® (aldesleukin) Breakthroughs in Cancer Immunotherapy Development 2015 2018 First CAR-T Cell](https://reader033.vdocuments.mx/reader033/viewer/2022060506/5f1f3559558e493ca7252aa6/html5/thumbnails/28.jpg)
28
COBRA™ Pipeline
SINGLE FOCUS ON DEVELOPING T CELL ENGAGING THERAPIES
![Page 29: Pioneering the Next Generation of Redirected T Cell ......renal cell carcinoma PROLEUKIN® (aldesleukin) Breakthroughs in Cancer Immunotherapy Development 2015 2018 First CAR-T Cell](https://reader033.vdocuments.mx/reader033/viewer/2022060506/5f1f3559558e493ca7252aa6/html5/thumbnails/29.jpg)
29
COBRA™ Platform Pipeline
ExpectedQ1 2021
ExpectedH2 2021
![Page 30: Pioneering the Next Generation of Redirected T Cell ......renal cell carcinoma PROLEUKIN® (aldesleukin) Breakthroughs in Cancer Immunotherapy Development 2015 2018 First CAR-T Cell](https://reader033.vdocuments.mx/reader033/viewer/2022060506/5f1f3559558e493ca7252aa6/html5/thumbnails/30.jpg)
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
![Page 31: Pioneering the Next Generation of Redirected T Cell ......renal cell carcinoma PROLEUKIN® (aldesleukin) Breakthroughs in Cancer Immunotherapy Development 2015 2018 First CAR-T Cell](https://reader033.vdocuments.mx/reader033/viewer/2022060506/5f1f3559558e493ca7252aa6/html5/thumbnails/31.jpg)
31
Thank You