MRC Technology Accelerating the discovery and development of novel - - PowerPoint PPT Presentation

Dr Kerstin Papenfuss Therapeutics Review Team Leader

MRC Technology

Accelerating the discovery and development of novel cancer therapeutics: Keytruda and beyond

Forming partnerships to drive early stage scientific research to the patient

ACADEMIC AND NON PROFIT

Institutions

PHARMACEUTICAL BIOTECHNOLOGY

Markets

MRC heritage

established 2000

CHARITY status 140+ staff

New PARTNERSHIPS Therapeutic antibodies Small molecule drugs 10 drugs in development ≈£20M Annual Rev 4 drugs on the market

Preclinical development Clinical Trials Market Approval

De-Risking Targets

Target identification & Validation

Increased R&D costs Pharma downsizing

Increased R&D costs

Based at the Stevenage BioCatalyst Open Innovation Campus, UK A purpose built MRCT facility

• pened in April 2016

> 90 scientists State-of-the-art equipment and capabilities Chemistry and antibody engineering teams in one place

• ffers unique flexibility

The Centre for Therapeutics Discovery

HTS Screening Compound Libraries Rational drug design Assay Development Medicinal Chemistry Antibody Generation

Assay development Hit generation Lead Identification Lead Optimisation

ADME Antibody Engineering

The Centre for Therapeutics Discovery

Therapeutics on the market

Humanising for over 25 years using MRC’s technology 56 antibodies humanised 4 currently on the market

ATP in PknB Tamiflu in N1

Keytruda...

One of the first IO drugs on the market Immuno-oncology (IO) è Paradigm shift in cancer treatment

q

Immuno-oncology therapies are medicines that use the body’s immune system to fight cancer

q

They target the body’s immune system, not the tumour itself

q

They enable the immune system to selectively recognise and attack cancer cells Keytruda (Prembrolizumab) è T-cell checkpoint inhibitor

q

Binds to PD-1 and blocks PD-1 binding to its ligand

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PD-1 is a T-Cell receptor that acts to ‘suppress’ T-Cell activity when it binds PD-1 ligand (a natural ‘brake’ on the immune system)

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PD-1 ligand is expressed on the surface of many tumours

q

So tumours protect themselves against T-Cell attack by local suppression of the immune system

Keytruda...how did we get involved?

MRCT’s Antibody Humanisation Service Organon were acquired by Schering-Plough Corporation in March 2007 (US$14.4b) Schering-Plough were acquired by MSD in November 2009 (US$41.1b) Interestingly the antibody doesn’t feature as a significant asset in either deal!

2014

First FDA approval

2008

delivery of humanised ab

2007

Deal signed è Project payment; clinical success payments; royalty on product sales

2006

Presentation on antibody humanisation to Organon at BIO

Keytruda…now

Approved for: Stage IV melanoma, Metastatic NSCLC, Metastatic HNCC In clinical trials: 442 in total

…and beyond

MRCT’s reaction to IO paradigm shift Opportunistic qRe-evaluate current cancer assets in IO context qConsider IO context for novel cancer projects Strategic: Immuno-Oncology Alliance with Cancer Research Technology qidentify and validate novel drug discovery targets that could lead to new immunotherapy treatments

MRCT cancer portfolio

ULK1 Cancer autophagy MRC ALK ADC Cancer Internal MNK inhibitor Cancer Southampton Uni PAICS inhibitor Cancer Netherlands Cancer Institute

Hit Generation Lead Assay Development Hit to Lead

Matriptase Osteoarthritis Newcastle University MALT1 Cancer University of Lausanne

Plexin B1 antibody Osteoporosis and cancer Max Planck Institutes

Confidential Cancer MRC CD36 Metastatic cancer IRB Barcelona

Opportunistic: MNK1 in IO

Direct cancer target: MAP kinase-interacting serine/threonine kinase, which is activated by RAS and MAPK signaling pathways and is involved in regulation of protein translation. MNK1 is linked to cell transformation and tumorigenesis MRCT lead series: Selective, stable Target engagement ü in vitro ü in vivo Emerging data from competitor have identified MNK1 as Immuno-

• ncology target, showing T cell dependent anti-cancer effects in vivo

and combination potential with PD-1 targeting drugs è we are now re-investigating our compounds in the context of similar IO models

Strategic: Alliances with Cancer Research Technology

MRCT investment into CRT Discovery Labs brings together Cancer Research UK’s network of leading scientists with CRT’s cancer-focused validation expertise and our antibody screening and development capability New targets that increase cancer’s susceptibility to the immune system will be identified from Cancer Research UK’s funded research Aims to identify targets for the development of both antibody (MRCT) and small molecule therapeutics (CRT) Focus on early stage target validation carried out by CRT Validated targets will then enter into the respective company pipelines Still seeking a clinical partner to accelerate the progress of promising compounds into the clinic

www.callfortargets.org

Kerstin Papenfuss

Therapeutics Review Team Leader, MRC Technology

kerstin.papenfuss@tech.mrc.ac.uk - www.mrctechnology.org

THANK YOU!