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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*
2
1
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MabVax Therapeutics
eTherRNA
* In no particular order
Jounce Therapeutics
BeneVir
VEL Vaccines Biosciences
Ganymed
Agenus
13
Psioxus Therapeutics
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15
immunotherapyforum.com | Phacilitate
15 Immuno-oncology biotechs to watch in 2017*
12
11
* 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 - [email protected] 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:[email protected]
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