blinkbio short intro deck 30oct2017 final · coupled to the rapid systemic clearance of the parent...

Summary Presentation

October-2017: Non-Confidential

BlinkBio: Tunable Drug Conjugates (TDCs)Differentiated Drug Conjugate Therapies§ Antibody Drug Conjugates (ADCs) have established the potential value of

the targeted delivery of toxins as an important class of anti-cancer therapies but there is still significant room for improvemento ADCs stay in the body for days-to-weeks, complicating the management of on-target and off-

target toxicityo Conversely, the large MW of ADCs limits tumor penetration and optimal efficacyo Heterogeneity of target receptor expression in tumors can further mitigate efficacy

§ We have designed Tunable Drug Conjugates (TDCs) based on the concept that the rapid and uniform release of toxin payloads inside tumors, coupled to the rapid systemic clearance of the parent TDC after dosing, will improve Therapeutic Index (T.I.)

§ We have assembled a suite of component technologies with properties that align around this goalo Various ligands can be employed with proprietary silicon-based linkers (SiLinkers) and novel

Payload Cassette (PC) designs that can be preferentially coupled to Conditionally Active Payloads (CAPs)

Non-Confidential – October 2017

2

Continued Expansion of the DC Field Implies an Important Ongoing Role in the Treatment of Cancer

§ Four FDA approved therapies – Kadcyla (Genentech), Adcetris(Seattle Genetics/Takeda) and Besponsa & Mylotarg (both Pfizer) -plus seven ADCs in Phase III trials indicate a growing presence o Sales of Kadcyla and Adcetris alone totaled ~$1.4 billion in 2016*

§ Partnering Deal flow and Financing activity demonstrate Pharma and investor interest in the space – especially for companies with innovative components o Candidate partnership deals: IMGN and Jazz Pharma’s Collaboration/Option

deal provides IMGN with $75 MM upfront fee, $100 MM in development funding, plus milestones and royalties for three pipeline products

o Technology partnership deals: Abzena licensed it’s ThioBridge linker technology to OBI Pharma for a fee, up to ~$170 MM in milestone payments, and royalties

o Funding deals: Mersana’s $75 million IPO and current ~$400 million Market Cap is based on ADCs utilizing their innovative fleximer payload technology


3* - based on reported sales of Seattle Genetics ($) and Takeda (¥) for Adcetris and Roche (CHF) for Kadcyla with estimated Fx

TDC Components Are Designed to Deliver Our Rapid Payload Release/Rapid Systemic Clearance Goal

§ SiLinkers provide tunable linker chemistries with systemic stability and rapid, uniform release of silanol-containing payloads in a pH-dependent mannero Good stability at 37oC at pH7.4 with rapid &

tunable hydrolysis rates at endosomal/tumor microenvironment pH (~5.5 to 6.5)

§ Payload Cassettes (PC) enable uniform release of both multiple and mixed payloads to drive higher intracellular concentrations

§ The optional use of pH dependent Conditionally Active Payloads (CAPs) can further enhance T.I.


The SiLinker and Payload Cassette Platform

4

Small Molecules (SM), antibody fragments, or antibodies* can be used as ligands

* - as an option for stable payload cassettes in ADC applications

Key Advantages of Our Unique TDC Platform

§ Enhancing Efficacyo pH sensitive SiLinkers for rapid & uniform release of payloads inside targeted cells

and in the acidic microenvironments of solid tumors o Targeting with Small Molecule (SM) or antibody fragment ligands will allow better

tumor penetration compared to traditional ADCs

§ Reducing Toxicityo SM or antibody fragment ligands allow systemic clearance of TDCs in hours –

allowing patient specific schedule adjustments to help manage on and off target toxicities

o Conditionally Active Payloads (CAPs) have reduced toxicity against normal cells due to the poor permeability of these payloads at physiological pH, but exhibit efficient permeation of cell membranes at the acidic pH’s that cause SiLinkercleavage in the endosome/lysosome and in the acidic tumor microenvironment


5

Our TDCs have a unique set of attributes that combine to produce adifferentiated rapid payload release/rapid systemic clearance profile

Combination of an Expansive Toolbox and a Quality Lead Candidate Program Provides a Strong Position From Which to Move Forward


6

§ Our modular toolbox is providing multiple spacers; adaptor configurations for payload cassettes; SiLinkers with varying cleavage characteristics; and silanol-payload analogs, including Conditionally Active Payloads (CAPs).

§ Establishes breadth & depth of the Core Platform and facilitates rapid lead optimization

§ For our Lead FRα project, next generation TDCs with multiple different linker types, payload cassette configurations and CAPs are part of a lead optimization project that is geared toward an IND track candidate in 1Q2018 and an IND filing in 1Q2019

At 30 minutes, pictures from different fields show overlap of the dyes at the cell surface but separation of red and green dyes inside cells - consistent with the rapid cleavage rate of our pH sensitive linkers

SiLinkers Demonstrate Rapid Payload Release After Internalization into Cells Using a Model TDC


SM-FRαLigand

BODIPY

Rhodamine

Linker cleavage at endosomal pH separates the two dyes

ModelTDC

7

Folate Receptor Targeting ProjectValidated Clinical Activity and a Strong Rationale


8

§ FRα is overexpressed in various cancers, notably Ovarian and NSCLC, and is a clinically validated target o ImmunoGen’s IMGN853 (Mirvetuximab Soravtansine) and ONX-0801/BTG-945 provide

clinical Proof-of-Concept (PoC)

§ FRα undergoes significant recycling after internalization making it a good choice for our endosomally cleaved SiLinker TDCs

§ Known heterogeneity of FRα expression between & within tumor lesions can be addressed by an enhanced bystander effect resulting from SiLinker cleavage in the acidic core of the tumor microenvironment

§ Rapid release of payloads from payload cassettes provides a route to superior efficacy; and, targeted delivery of CAP payloads will avoid pulmonary toxicity of BTG-945

§ Our early SM-TDC prototypes containing Vinblastine Silanol (VS) payloads exhibited compelling in vivo activity without body weight loss

DMPK Evaluation of SM-TDCs in Mice Fit OurPreferred Rapid Clearance Profile


9

SM-TDC SiLinker Type Plasma Stability (H/R/M)

% Remaining (24h)

Dose (mg/kg)

T1/2 (h) Cl (mL/min/kg)

AUC (h*ng/mL)

Vss(L/kg)

BB-01 Pyrimidine TBD 5 3.3 0.12 717,557 0.02

BB-03 Pyrimidine TBD 5 4.1 0.11 770,689 0.05

BB-11 Pyrimidine 25/36/77 5 2.8 0.08 1,016,127 0.02

BB-20 Phenyl 100/100/100 5 11.4 0.12 716,717 0.10

BB-42 Pyrimidine 100/100/91 5 11 0.16 534,897 0.12

0 4 8 1 2 1 6 2 0 2 4

0

2 5

5 0

7 5

1 0 0

T i m e ( h r )

Pla

sm

a C

on

ce

ntr

ati

on

(µg

/mL

)

B B - 4 2 , 1 µ m o l / k g

M M A F - S

§ Small Molecule ligand TDCs (SM-TDCs) exhibit good plasma stability, excellent exposures, low volumes of distribution, and clearance rates between 3-12 hours o Compared to clearance rates measured in days for

ADCs - confirming likely scheduling advantages§ Single dose PK data for BB-42 (an MMAF

containing TDC) in C57-Black mice show minimal systemic release of payload over 24 hours

BB11, a VS-Containing FRα-TDC, Has Compelling In Vivo Activity and is Well Tolerated in Xenograft models


BB-11, an active folate targeted TDC with a triple Vinblastine Silanol (VS) payload cassette, provides compelling in vivo Proof-of-Concept in both KB and OV90 xenograft models § BB-11 is well tolerated and demonstrates significant tumor regression & cures in mouse xenograft models§ Three times per week regimen resulted in 5/5 cures and once weekly regimen gave 4/5 cures in KB xenograft models

10

KB Model (High FR expression) OV90 Model (Moderate FR expression)

0 5 1 0 1 5 2 0 2 5 3 0 3 50

2 0 0

4 0 0

6 0 0

8 0 0

1 0 0 0

1 2 0 0

1 4 0 0

D a y s

Tu

mo

r V

olu

me

(mm

3)

a. Anti-tumor activity

0 4 8 1 2 1 6 2 0 2 4 2 8 3 2 3 60

1 0 0

2 0 0

3 0 0

4 0 0

D a y s

Tu

mo

r V

olu

me

(m

m3

)

a. Anti-tumor activity

0 5 1 0 1 5 2 0 2 5 3 0 3 58 0

9 0

1 0 0

1 1 0

D a y s

No

rma

lize

d B

W (

%)

b. Body Weight Loss (tolerability)

0 5 1 0 1 5 2 0 2 5 3 0 3 5 4 0 4 58 0

9 0

1 0 0

1 1 0

D a y sN

orm

ali

zed

BW

(%

)

b. Body Weight Loss (tolerability)

Vehicle Control

BB-11: 1µmol/kg, TIW for 2 weeks

BB-11: 3µmol/kg, QW for 2 weeks

Schedule

Building on Prototype TDC Data: Design Considerations to Enable Accelerated IND-Track Candidate Selection


11

0 4 8 1 2 1 6 2 0 2 4 2 8 3 2 3 6 4 0 4 40

3 0 0

6 0 0

9 0 0

1 2 0 0

1 5 0 0

D a y s

Tu

mo

r V

olu

me

(m

m3

)

Single Payload TDCTGI/no regression

Triple Payload TDC Regression & 1 cure on day 45

Vehicle Control

0 .0 1 1 1 0 0 1 0 0 0 00

2 0

4 0

6 0

8 0

1 0 0

C o n c e n tra tio n (n M )

% P

rolif

erat

ion Non-targeted MMAF-S delivery (2 h

exposure) – no cytotoxic effects

Targeted MMAF-S delivery (2 h exposure) – potent cytotoxic effects

P yr im id in e C a r b o x a m id e P h e n yl0

2 0 0

4 0 0

6 0 0

8 0 0

1 0 0 0

1 2 0 0

1 4 0 0

t 1/2

(m

in)

p H 7 .4

p H 5 .0

Stable at pH7.4, rapid hydrolysis at acidic pHs

§ Use of Payload Cassette (PC) constructs:Superior in vivo efficacy compared to singlepayload constructs at doses that deliverequivalent amounts of payload

§ Use of Conditionally Active Payloads (CAPs) as means to improve Therapeutic Indexo Thymidylate Synthase Inhibitor Silanol (TSI-S)o Monomethyl Auristatin F Silanol (MMAF-S)o “SN38-Silanol” (SN38-S)

§ Use of SiLinkers with more rapid pH-dependent hydrolysis profiles due to known recycling behavior of Folate Receptor

§ Modular approach profiling selected spacers and adaptors for final construct assembly

Our Business Strategy§ We intend to seek investor and/or partner funding in order to

advance our lead FRα program through pre-clinical and early clinical development o This could involve partner participation in a $15-20 million Series B round

or an upfront fee/milestone/royalties structure for regional commercial rights to a successful FRα-targeted TDC

§ We intend to execute partnerships to provide near term validation of the platform and a broadening of our pipeline o Target based partnerships (collaborations based on individual targets

with typical fee/milestone and royalty or regional rights structures)o Technology based partnerships (e.g. deployment of pieces of the

platform in a partner’s pre-existing Drug Conjugate projects)

§ Longer term, we are targeting liquidity for investors via either a Merger/Acquisition exit or an IPO


12

Summary


13

§ We innovated TDCs with a set of novel technologies possessing an aligned set of properties designed to fit a differentiated rapid payload release/rapid systemic clearance approach that we believe can provide a compelling addition to existing Drug Conjugate technologies

§ Tunable PK profile allows for systemic clearance in hours (vs. days-to-weeks for ADCs) enabling clinical management of side-effects through dose and schedule adjustments

§ Conditionally Active Payloads (CAPs) are ideally suited as payloads for TDCs, because aligned pH properties can further increase Therapeutic Index (TI) by releasing CAPs within the acidic microenvironment of solid tumors

§ We have a business model that focuses on the development of a FRαtargeted TDC through clinical validation while broadening the deployment of our TDC platform through collaborative discovery, technology and development partnerships

BlinkBio Inc.Tunable Drug Conjugates: Holistically Redesigned

Drug Conjugates

Management Bio’s

October-2017: Non-Confidential

Colin Goddard, Ph.D.Chairman & CEO

Colin Goddard is an investor in the company and has been part of the leadership team since the inception of BlinkBio in 2015. Dr. Goddard was formerly CEO of OSI Pharmaceuticals for 12 years, raising over $1.5 billion and overseeing the development, launch and commercialization of the lung cancer drug Tarceva through to OSI’s $4 billion acquisition by Astellas. He also Chairs the board of Mission Therapeutics and is a board member of the drug conjugate company Endocyte (NASDAQ:ECYT). Dr.Goddard obtained his PhD in cancer chemotherapy in the UK and completed post-doctoral training at the National Cancer Institute in Bethesda, MD.


15

Maneesh Pingle, Ph.D.President

Maneesh Pingle has been part of the leadership team since the inception of BlinkBio in 2015 and oversees business development and operations. He brings a multidisciplinary scientific background with training in pharmacy, medicinal and nucleic acid chemistry and molecular biology. Dr. Pingle received his Ph.D. from Purdue University and his Bachelor’s degree in Pharmacy from the Bombay College of Pharmacy (India).


16

Jutta Wanner, Ph.D.Vice-President, Research

Jutta Wanner has also been part of the leadership team since inception andis an experienced pharmaceutical industry executive having joined BlinkBiofrom Roche in Nutley, NJ where she was a co-lead in discovery chemistry.She brings expertise across multiple therapeutic areas including oncology,inflammation and virology. Dr. Wanner received her PhD from the Universityof Kansas and conducted her postdoctoral training at The Scripps ResearchInstitute in San Diego.


17

blinkbio short intro deck 30oct2017 final · coupled to the rapid systemic clearance of the parent...

Documents