IMMUNO-ONCOLOGY

BIOTECHS TOWATCH IN 2017

i m m u n o t h e r a p y f o r u m . c o m

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Immunocore

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Immodulon

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7 memgen

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immunotherapyforum.com | Phacilitate

Immuno-oncology biotechs to watch in 2017*

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MabVax Therapeutics

eTherRNA

* In no particular order

Jounce Therapeutics

BeneVir

VEL Vaccines Biosciences

Ganymed

Agenus

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Psioxus Therapeutics

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immunotherapyforum.com | Phacilitate

15 Immuno-oncology biotechs to watch in 2017*

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* In no particular order

Targovax

Syndax Pharmaceuticals

F-Star

TapImmune

16 Apogenix

VEL VACCINES BIOSCIENCESCEO: RICHARD JANECZKO, PHD

DISRUPTIVE BIOTECHS | 1

VEL vaccines is an early stage, pre-clinical,

biopharmaceutical company focused on the

development of synthetic immune-based

therapies for the treatment of cancer and

complex infectious diseases.

The antigenic variability of tumour cells can

lead to a dynamic shift in the cancer epitope

landscape, along with escape from the immune

system by down-regulating tumour antigen

expression/presentation and inducing immune

tolerance. The concept behind the VEL vaccines

are to construct a super-complex combinatorial

mixture of immunogens which represent actual

and potential antigenic composition of

antigenically variable targets (AVTs) as they

mutate.

VEL vaccines unique focus was highlighted in an

interesting 2014 paper 'Variable epitope

library carrying heavily mutated survivn-

derived CTL epitope variants as a new class of

efficient vaccine immunogen tested in a mouse

model of breast cancer', submitted to the

journal Human Vaccine Immunotherapy.

It was demonstrated in this 2014 paper that

immunogens carrying large combinatorial

libraries of mutated epitope variants induce

potent, broad, and long lasting CD8+IFN-y+ T

cell response, as well as HIV-neutralizing

antibodies. In the proof-of-concept study, the

immunogenic properties and anti-tumour

effects of the VELs bearing survivn-derived CTL

epitope variants in an aggressive metastatic

mouse 4T1 breast tumour model. Statistically

significant tumour growth inhibition was

observed in immunized mice in both

prophylactic and therapeutic settings. These

vaccinated mice developed epitope-specific

spleen cell and CD8+ IFN-y+ T cell responses

that recognize more than 50% of the panel of

87 mutated epitope variants.

This early data showed the feasibility of the

application of VEL vaccines as an alternative

approach for the development of molecular

vaccines against cancer.

Founded in 2016Based in Las Vegas, NV, USA

GANYMED

DISRUPTIVE BIOTECH | 2

Ganymed is aiming to revolutionize cancer

treatment by developing a new class of

therapeutic drug called Ideal Monoclonal

Antibodies (IMABs).

IMAB362 is a first-in-class antibody drug being

developed for the treatment of

gastroesophageal and other solid cancers. The

therapy is highly specific and selective for the

tight junction protein Claudin-18.2 (CLDN

18.2). CLDN18.2 is expressed in stomach cells

only and its overexpressed in up to 80% of

gastrointestinal adenocarcinomas and 60%

pancreatic tumours in addition to other solid

tumours. The investigative therapy received

orphan drug designation in the US and Europe

for gastric and pancreatic cancers and in a

phase II trial extended median overall survival

by 4.8 months when added to standard

chemotherapy in patients with advanced gastric

cancer (results in July 2016).

Based on the groundbreaking initial research by the

company's founders (below), the firm has set itself the

goal of revolutionizing the immunotherapy field

through a translational science platform, which couples

the choice of target mechanisms to potential predictive

biomarkers of response. It's lead product, JTX-2011, a

monoclonal antibody targeting the ICOS receptor that

is designed to both stimulate T effector cells and

reduct T regulatory cells in tumours, thus shifting the

balance of the tumour microenvironment from

immunosuppressive towards anti-tumour activity.

In April 2016, Jounce Therapeutics presented new

preclinical data on two of its programs at the American

Association of Cancer Research (AACR) Annual

Meeting in New Orleans. The first presentation was

focused on it’s humanized ICOS (inducible co-

stimulator molecule) agonist antibody, JTX-2011,

being developed for the treatment of solid tumours.

JTX-2011 has a dual mechanism of action, stimulating

T effector cells and selectively reducing intra-tumoral

T regulatory cells, thereby shifting the balance of T

cells in a tumour towards anti-tumour activity.

Founded: 2013Based: Cambridge, MA, USA

LEAD PRODUCT:IMAB 362 (GASTROESOPHAGEAL CANCER)

JOUNCETHERAPEUTICS

CEO: RICHARD MURRAY, MDFOUNDERS:JAMES P.ALLISON, PHD,CHAIR, UNIVERSITY OF TEXASANDERSON CANCER CENTERTHOMAS GAJEWSKI,MD,PHD,PROF, DEPT OF PATHOLOGY& MEDICINE, UNIVERSITY OF CHICAGODREW PARDOLL, MD, PDH, DIRECTOR, CANCERIMMUNOLOGY, SIDNEY KIMMEL COMPREHENSIVECANCER CENTER, JOHNS HOPKINS UNIVERSITY SCHOOLOF MEDICINEROBERT SCHREIBER, DIRECTOR, CENTER FOR HUMANIMMUNOLOGY & IMMUNOTHERAPY, WASHINGTONUNIVERITY SCHOOL OF MEDICINEPADMANEE SHARMA, MD, PHD, PROF, DEPT OFGENITOURINARY MEDICAL ONCOLOGY, UNIVERSITY OFTEXAS MD ANDERSON CANCER CENTERLOUIS WEINER, MD, DIRECTOR, GEORGETOWNLOMBARDI COMPREHENSIVE CANCER CENTER

LEAD PRODUCT:ICOS AGONIST PROGRAM ‐ JTX‐2011

At the same gathering, the company presented on its

Translational Science Platform which had discovered

that TIM-3 and LILRB2, a novel protein-to-protein

binding pair on human macrophages, could be

converted to immune-suppressive macrophages to

immune-enhancing macrophages, those providing a

new therapeutic opportunity.

This July, Jounce Therapeutics made headlines by

announcing a collaboration with Celgene

Corporation, worth a potential $2.3 billion in

milestone payments and $225m for early phase work.

The focus of this partnership is to develop and

commercialize the cancer tumour treatment, JTX-

2011, along with other immunotherapies.

Founded: 2001Based: Mainz, Germany

CEO: DR OZLEM TURECISCIENTIFIC ADVISORY BOARD:PROF DR UGUR SAHIN, FOUNDER & CEO, BIONTECHAG & DIRECTOR, TRON-TRANSLATIONAL ONCOLOGY,JOHANNES GUTENBERG UNIVERSITY MAINZPROF DR HANS HENGARTNER, FEDERAL INSTITUTEOF TECH ETH ZURICH, UNIVERSITY OF ZURICHPROF DR ROLF ZINKERNAGEL, UNIVERSITY OFZURICHDR ULRICH GRANZER, CO-FOUNDER, EURAGDR BJORN HOFFSTEDT, CO-FOUNDER, EUROPEANSOCIETY OF MICROBIOLOGY AND INFECTIOUSDISEASES

BENEVIR

DISPRUTIVE BIOTECHS | 3

Oncolytic viruses represent a new class of

therapeutic agents that promote anti-tumour

responses though a dual mechanism of action that

is dependent on selective tumour cell killing and

the induction of systemic anti-tumour immunity.

Imlyic, Amgen's genetically modified herpes

simplex virus type 1, was the first of these new

therapeutics to be approved in 2015.

Benevir, a Maryland cancer vaccine upstart, claims its

platform, T-Stealth, "overcomes a major barrier to the

clinical success of oncolytic viruses". The platform

'hides' the therapeutic from the host's immune system,

which can't recognize between a 'good' virus (i.e one

sent to kill cancer), and a bad one (such as influenza).

Because the oncolytic immunotherapy can hide from

anti-viral T-cells, the T-Stealth viruses mitigate

antagonism between oncolytic viruses and immune

checkpoint inhibitors. This allows these two types of

therapeutics to be administered simultaneously and a

synergistic clinical response can be maximized.

Founded: 2011Based: Gaithersburg, Maryland, US

IMMUNOCORE

Immunocore was founded in 2008 as a spinout of

German Medigene AG who had acquired former

Avidex in 2006, which was founded in 1999 as a

spinout from the University of Oxford by Dr Bent

Jakobsen.

Immunocore’s proprietary technology is focused on

small protein molecules called ImmTACs (Immune

mobilising mTCR Against Cancer) that enable the

immune system to recognise and kill cancerous or

bacterially/virally infected cells. Immunocore's

ImmTACs, a new class of drug with ultra-high

affinity for intracellular cancer targets, are

synthetic, soluble T cell receptors (TCRs) that

recognise diseased cells containing disease specific

targets.

In January 2016, its lead ImmTAC therapeutic,

IMCgp100, was granted Orphan Drug

Designation by the US FDA for Uveal

melanoma, a rare disease in which cancer cells

form in the tissues of the eye. In 2015,

IMCgp100 was accepted to be part of the

EMA’s Adaptive Pathways Pilot Programme.

In 2013, Immunocore had GSK and Genentech

pay for rights to it’s pre-clinical drugs (£142m &

$10-$20m, up to $300m respectively) targeting

several therapeutic targets. This was followed

by a January 2014 deal with MedImmune, who

made a upfront payment of $20 million and

pledged up to $300 million in development and

commercial milestone payments.

FOUNDERS:MATTHEW MULVEY, PHD,KATHERINE SACKSTEDER, PHDIAN MOHR, PHD

CEO: ELIOT FORSTER, PHD

Founded: 2008Based: Abingdon, Oxon, UK

LEAD PRODUCT:IMCGP100 ‐ ENTERING PHASE 111 ‐ UVEALMELANOMA

IMCGP100 CHECKPOINT COMBINATION ‐ENTERTING PHASE 111 WITH ASTRAZENCA ‐CUTANEOUS MELANOMA 

DISRUPTIVE BIOTECH | 4

MabVax uses its discovery platform to survey the immune

response of patients by interrogating single B-cells from

these patients who are producing antibodies against the

intended target. These antibodies are then cloned and

produced recombinantly. HuMab-5B1 (mvt-5873) is the

company’s lead clinical development product and currently

in a Phase I clinical trial in patients with metastatic

pancreatic cancer. Trials are also evaluating MVT-2163, also

based on HuMab-5B1 antibody, as a next-generation PET

imaging agent for the diagnosis and management of patients

with pancreatic cancer.

Memgen's lead product, ISF35, is a first-in-

class, T-cell cancer immunotherapy that

promotes an anti-tumour immune response.

Direct intratumoral delivery of ISF35, a non-

replicating adenovirus encoding CD40 ligand,

activates tumour-specific T cells through

immunostimulation of dendritic cells. The anti-

tumour immune response complements

checkpoint inhibitors and

CEO/President: J. David Hansen

Founded: 1988Based: San Diego, CA, USA

MABVAX THERAPEUTICS

MEMGEN

LEAD PRODUCT:MVT‐5873 ‐ PHASE 1 ‐ PANCREATIC AND COLON CANCERS

MVT‐2163 ‐ PHASE 1 ‐ PANCREATIC AND COLON CANCERS

In January 2016, it was granted Orphan Drug

Designation for the treatment of uveal

melanoma and in 2015 it was accepted to

participate in the European Medicine Agency's

(EMA) Adaptive Pathways Pilot

Programmes. Additionally a phase I/II clinical

trial of ISF35 and Keytruda in refractory

metastatic melanoma is being launched at MD

Anderson Cancer Center.

CEO: Robert Coates, PhDPresident: Mark Cantwell, PhD

Founded: 1999Based: Houston, TX, USA

LEAD PRODUCT: ISF35METASTATIC NON‐SQUAMOUS NON‐SMALL CELL LUNGCANCER WITH NEGATIVE PD‐L1 EXPRESSION (PH1)HEPATOCELLULAR CARCINOMA REFRACTORY TOCONVENTIONAL THERAPIES (PH1)ADVANCED/METASTATIC BLADDER CANCER (PH1)METASTATIC MELANOMA REFRACTORY TO CHECKPOINTINHIBITORS (PH1/2)

IMMODULON THERAPEUTICSDISRUPTIVE BIOTECHS | 5

In 2007, Charles Akle, a renowed surgeon, set up the

company following a large donation from former patients to

allow him to embark on new research. The result has been

the development of IMM-101, a immunotherapy containing

a heat killed whole cell Mycobacterium which engages with

the immune system to combat malignancy.

IMM-101 has been shown to enhance Type 1 immunity and

increase functional CD8+ cytotoxic T-cell activity in vivo in

preclinical models of cancer. It has received Orphan Drug

Designation in the USA and EU for the treatment of

pancreatic cancer.

eTherRNA

Founder/Executive Chairman: Dr Charles Akle

Founded: 2007Based: Houston, TX, USA

LEAD PRODUCT: IMM‐101 ‐ PANCREATIC CANCER

CEO: Prof Kris Thielemans

Founded: 2013Based: Niel , Belgium

LEAD PRODUCT: TRIMIX ‐ PHASE II  ‐  MELANOMA

The focus of eTherRNA is to boost the immune

response through the dendritic pathway. The

company's lead product, TriMix, contains three

naked mRNA molecules:

- caTLR4 (activating DC presentation of

antigens to CD4/CDB T cells)

- CD40L (induces DC stimulation of antigen-

specific action of CD4 T-cells)

- CD70 (induces DC simulation of CD8 T cells)

When DCs are simply loaded ex vivo with

tumour associated antigen, it doesn't induce a

robust immune response in which patients

demonstrate clinical benefit. Investigations

involving TriMix are now being reviewed,

(preclinical and phase I/IIa studies in advanced

melanoma) to see if they can overcome these

limitations.

AGENUS

Agenus is an immuno-oncology company developing

antibodies including checkpoint inhibitors and modulators, and

cancer vaccines. The company was founded in 1994 and

pioneered immunotherapies, including heat shock protein-

based cancer vaccines, a program that has developed into its

Prophage Series of personalized anti-cancer vaccines. In 2000

Agenus acquired Aquila Biopharmaceuticals and a year later it

acquired Aronex Pharmaceuticals. In February 2014 the

company acquired a European firm, 4-Antibody, along with

their portfolio of checkpoint modulators (CPMs) and a

platform (Retrocyte Display® technology) to rapidly and

efficiently discover new antibodies.

In June 2016 it started recruiting for a Phase I/2 clinical trial

for its anti-GITR agonist antibody INCAGN1876, which targets

the glucocorticoid-induced TNFR-related protein, or GITR.

Upon activation, GITR, a co-stimulatory receptor, can

stimulate immune cells to target and potentially destroy

cancer cells. This antibody was discovered during an earlier

collaboration with Ludwig Cancer Research. INCAGN1876 is

being co-developed with Incyte.

CEO/Chairman: Garo Armen, Phd

Founded: 1994Based: Lexington, MA, USA

LEAD PRODUCTS: CTLA‐4 (ANTAGONIST) ‐  PH1GITR (AGONIST) ‐  PH1

F-STAR

DISRUPTIVE BIOTECHS | 7

This biotechnology company was originally

founded in Vienna and its current main

research site is in Cambridge, UK. The company

is focused in developing bispecific monoclonal

antibodies using a modular combinatorial

approach that engineers the Fc constant region

of an immunoglobulin into a novel antigen-

binding site.

Its lead immuno-oncology product is pre-

clinical candidate – FS118 mAb2 – which can

target two checkpoint inhibitors, with the

potential to deliver greater efficacy and

tolerability than combinations or

monotherapies across a wide range of tumours.

TAPIMMUNE

TapImmune is a clinical-stage immuno-oncology

company specializing in the development of

innovative peptide and gene-based

immunotherapeutics and vaccines for the

treatment of cancer & metastatic disease. In June

206, it reached the major milestone of dosing its

first patient in a Phase 2 trial for triple negative

breast cancer (does not express the genes for

estrogen receptor (ER), progresterone receptor

(PR) or Her2/neu) with its cancer vaccine TPIV

200, a Folate Receptor Alpha T-cell vaccine.

Founded: 2006Based: Cambridge, UK

LEAD PRODUCTS (IMMUNO‐ONCOLOGY): FS118 ‐ PRECLINICAL ‐ BISPECIFIC ANTIBODYAGAINST TWO CHECKPOINT INHIBITORS 

CEO/Chairman: Garo Armen, Phd

CEO/Chairman: Glynn Wilson. PhDPresident/COO: John Bonfiglio, PhD MBA

Founded: 1999Based: Seattle, Washington

LEAD PRODUCTS:

TPIV 200 (COMBO WITH CHECKPOINT INHIBITOR) ‐PHASE II  ‐  OVARIAN CANCERTPIV 200 ‐ PHASE II  ‐  TRIPLE‐NEGATIVE BREASTCANCERTPIV 200 (WITH MAYO CLINIC/DOD) ‐ PHASE II  ‐TRIPLE‐NEGATIVE BREAST CANCERTPIV 200 ‐ PHASE II  ‐  PLATINUM SENSITIVEOVARIAN CANCER TPIV 100/110 ‐ PHASE II  ‐  HER2/NEU BREASTCANCER 

Want to be part of our BiotechShowcase at the Phacilitate LeadersWorld Forum, alongside 240 VP/SVPspeakers from across the biopharmindustry?Email - michael@phacilitate.co.ukfor more details

TARGOVAX

DISRUPTIVE BIOTECHS | 8

Targovax is a Norwegian-based global biotechnology

company, dedicated to the design and development of

immunotherapy vaccines for application in post-

operation cancer treatments. The two treatment

approaches being invested are 1). A peptide-based

targeted immunotherapy platform for patients with

RAS-mutated cancers 2). A virus-based oncolytic

immunotherapy platform based on engineered

oncolytic viruses armed with potent immune-

stimulating transgenes for patients with solid tumours.

In 2015, the company merged with a fellow Nordic

biotech, Finland-based Oncos, enabling the combined

portfolio of clinical-phase immuno-oncology assets to

be brought through the clinic. Oncos lead product is a

Phase II-ready engineered human serotype 5

adenovirus ONCOS-102.

LEAD PRODUCTS:TG01 ‐PHASE 11 ‐ PANCREAS CANCER

Founded: 2010Based: Oslo, Norway/ Helsinki, Finland

CEO: Gunnar Gardemyr

Syndax is focused on developing an innovative

pipeline of combination therapies in multiple cancer

indications.

The company’s lead product candidate was granted

Breakthrough Therapy designation by the US FDA

following positive results from a Phase 2b clinical

trial, ENCORE 301, and is now being evaluated in a

Phase 3 clinical trial for advanced hormone receptor

positive breast cancer and as a combination

therapeutic in Phase 1b/2 clinical trials with Merck

& Co for non-small cell lung cancer and melanoma,

with Genentech for TNBC and with Pfizer + Merck

KGaA for ovarian cancer.

After a recent IPO, the company has secured an

exclusive global license to UCB’s UCB6352, a high

affinity antibody that binds to the CSF-1R. In

preclinical studies, inhibiting CSF-1R signalling

showed an anti-tumour immune response.

.

SYNDAXPHARMACEUTICALS

CEO: Dr Briggs Morrison

Founded: 2005Based: Waltham, MA, USA

LEAD PRODUCTS:E2112 (ENTINOSTAT + AROMASIN) ‐  PHASE III  ‐ ADV. HR+ HER2‐ BREAST CANCERJ1353 (ENTINOSTAT + OPDIVO + VIDAZA) ‐  PHASE11 ‐ NSCLCNCI‐7870 (ENTINOSTAT + PROLEUKIN) ‐  PHASE II  ‐RENAL CELL CARCINOMA

PSIOXUS THERAPEUTICSCEO: Dr John Beadle

Founded: 2010Based: Abingdon, Oxfordshire, UK

LEAD PRODUCT (IMMUNO‐ONCOLOGY):ENADENOTUCIREV ‐ PHASE IB ‐ COLORECTALCANCER

.Dr John Beadle co-founded PsiOxus in 2010

following the merger of two businesses which

he lead: Myotec Therapeutics and Hybrid

Biosystems. The company’s lead product,

enadenotucirev (EnAd) is an oncolytic virus,

which is a hybrid of Ad3 and Ad11p which has

undergone changes that render it unable to

replicate in normal cells. The virus selectively

propagates inside cancer cells, causing them

to die by membrane disruptive ‘lysis’. EnAd is

being evaluated in a number of different

cancers including colorectal, ovarian, bladder,

lung and renal cell carcinoma. These

investigations include the SPICE study (Phase

I, advanced epithelial tumours), the EVOLVE

study (Phase I/II, colorectal and bladder

cancer) and the OCTAVE study (Phase I/II,

platinum-resistant epithelial ovarian cancer).

Thank you for reading this short article highlighting new and disruptivebiotechs in Immuno-Oncology. I have no doubt that I have missed somevaluable inclusions. If you would like to point me to yours or othercompanies, please dont hesitate to email me at:nicholas.longworth@phacilitate.co.uk

Signing offNicholas LongworthHead of Content, Phacilitate

DISRUPTIVE BIOTECHS | 9

APOGENIX

.Apogenix’s pipeline focuses on the TNFSF-

dependent signalling pathway, with its lead

drug candidate, APG101, inhibiting the CD95

ligand, a molecule important in the

progression of solid tumours. Depending on

the target cell – immune cell or tumour cell –

the interaction between the CD95 ligand and

the CD95 receptor induces either apoptotic

cell death or invasive growth of cells.

Consequently, APG101 has a dual mechanism

of action. Currently APG101 is in a phase II

efficacy trial in recurrent gliobastoma and a

phase I trial for the treatment of

Myelodysplastic Syndromes (MDS).

Apogenix is also developing a companion diagnostic for

the newly -identified biomarker associated with the

CD95 ligand - the target of APG101 - to identify

glioblastoma patients who are most likely to respond

best to treatment.

Founded: 2005Based: Heidelberg, Deutschland

LEAD PRODUCT: APG1O1 ‐ PHASE II  ‐GLIOBLASTOMA

CEO: Dr Thomas Hoeger