XNK THERAPEUTICS Company presentation September 2021
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XNK THERAPEUTICS Company presentation September 2021
Disclaimer
IMPORTANT NOTICE
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conditions.
The information has been prepared solely for information purposes. The information in this presentation shall not constitute an offer to sell or the solicitation of an offer
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FORWARD LOOKING STATEMENTS
This presentation contains forward-looking statements that reflect management’s current views with respect to certain future events and potential financial
performance. Although XNK Therapeutics believes that the expectations reflected in such forward-looking statements are reasonable, no assurance can be given that
such expectations will prove to have been correct. Accordingly, results could differ materially from those set out in the forward-looking statements as a result of various
factors.
Important factors that may cause such a difference for XNK Therapeutics include but are not limited to: (i) the macroeconomic development, (ii) change in the
competitive climate and (iii) change in interest rate level.
This presentation does not imply that XNK Therapeutics has undertaken to revise these forward-looking statements, beyond what is required by applicable law or
applicable stock exchange regulations if and when circumstances arise that will lead to changes compared to the date when these statements were provided.
2
Today’s presenter
CEO
Johan Liwing
MSc In Engineering Physics
Experience
3
Company highlights
1. Built on world-leading research on NK cells at Karolinska Institutet in Stockholm
A unique, proprietary autologous NK-cell based platform with tangible
2. development potential
The platform has ideal properties for targeting cancer across a wide range of
3. indications in mono- and combination therapy
First-in-human phase I/II study showing very good safety data and promising
4. efficacy data for the leading investigational drug product
Phase II study ongoing in patients with Multiple myeloma in combination with
5. Sanofi’s anti-CD38 antibody Sarclisa (isatuximab)
A potential USD multi-billion white space market opportunity in the US and in
6. Multiple myeloma alone
4
Natural killer (NK) cells
- Natural ability to kill cancer cells
NK cell
Healthy cell
(inactive)
MHC
molecule
Inhibitory
receptor ▪ Discovered at Karolinska Institutet in 1975
▪ Play a major role in the host-rejection of
cancer cells
”OFF”
▪ Triggered by the lack of major
Activating Activating histocompatibility complex (MHC) receptors,
ligand receptor
often lost by cancer cells, and/or by
Cytotoxic
NK cell
overexpression of activating ligands
Cancer cell release
(active)
▪ NK cells release cytotoxic granules containing
Inhibitory
receptor
perforin and granzymes, killing the cancer
cells
”ON”
Activating Activating
ligand receptor
5NK-cell therapy at a tipping point
Promising market outlook Capital market momentum
▪ NK-cell therapy could be the Jul 2015 Mar 2020 Jul 2020 Jan 2021 Mar 2021 Apr 2021
next paradigm shift in cell- IPO AGC Inc. acquired IPO Collaboration deal Raised USD 9.0m to Research collaboration
USD 207m MolMed for USD USD 290m >USD 640m develop TCR-NK-
based cancer treatments 268m cell therapies
▪ Early clinical data for NK-cell
therapy points to high Oct 2013 Jun 2020 Dec 2020 Merger Mar 2021 Apr 2021 Jun 2021
complete response rates and a IPO Rights issue Raised USD 47m in Filed to raise Collaboration deal
USD 40m USD 90m series B financing to USD 100m in IPO >USD 2.3bn
better safety profile than CAR- advance pipeline
T treatments
▪ Additionally, NK-cell biology
has the promise to overcome
the barrier of targeting solid
tumours 2013 2015 2016 2017 2018 2019 2020 2021
▪ NK-cell therapies display an
increasing enthusiasm from
researchers and investors,
Jul 2015 Apr 2020 Aug 2020 Nov 2020 Mar 2021 Apr 2021
which has translated into IPO Collaboration deal Management buyout Sanofi offers to Secured USD 160m Raised USD 43m
significant investments USD 36m USD 3.1bn of remaining 45%
stake for USD 183m
acquire Kiadis for
USD 358m
Series C funding
from Casdin Capital
financing to advance
product pipeline
▪ Cell therapy companies
are transforming big
Jun 2020 Sep 2020 Feb 2021
pharma R&D Rights issue Research Collaboration deal
USD 201m collaboration USD 760m
6Autologous NK-cell therapies in clinical development
- XNK has a leading position in autologous NK-cell therapies
Selected indications Pre-clinical Phase I Phase II Phase III On market
Multiple myeloma
Hepatocellular
carcinoma
Non-small-cell lung
carcinoma
Glioblastoma
Colorectal
Breast
7Company history 2020 2020 2021 2021
Reports results First patient
SEK 64m recruited to the
from first-in- ODD status private phase II
human phase by the FDA placement combination trial
I/II clinical trial
completed
and initiates
2019 2020 planning for
phase II clinical
2017 Patent for Joins the trials
expansion of NextGenNK
2012 Patent granted in NK cells consortium
XNK Therapeutics the US for method granted in the
(then CellProtect to treat Multiple EU and Japan
Nordic myeloma with
2021
Pharmaceuticals)
is founded
expanded NK cells
2021 Dr. Johan
2020 Research Aschan and
Research collaboration Michael Uhlin
collaboration initiated with appointed as
Sanofi CMO and CSO,
2020 initiated with
Cellect respectively
Johan Liwing Biotechnology
is appointed
2011 2014 2018 as CEO
Patent granted ODD status
Cell therapy by EMA
for NK-cell
consortium
expansion in
initiated
the US and
China
8Our platform
- Step-by-step overview
1▪ Removal of blood sample from the
patient
6 1
2▪ Blood sample is frozen and
transported to XNK’s laboratory
3▪ Expansion and activation of NK cells
from peripheral blood of patients,
taking ~20 days
5 2
4▪ The activated NK cells are frozen, with
stability for up to 10 years
4 3 5▪ NK cells are transported to the patient
6▪ The activated NK cells are thawed and
infused to the patient without need for
further processing, with repetitive
dosing possible
9Expanded NK cells show cytotoxic effect
- Specifically targeted against autologous MM cells
Cytotoxic effect on MM cells Significant cytotoxicity against autologous MM cells
▪ Pharmacodynamic studies have Against autologous MM cells1) Against autologous non-MM
indicated that NK cells from 80%
cells1)
80%
patients with MM can be efficiently
expanded ex vivo
60%
▪ Expanded cells showed significant 60%
in vitro cytotoxicity against
autologous MM cells
% Lysis
% Lysis
40% 40%
▪ No significant toxicity against non-
MM cells
20% 20%
0% 0%
0.3:1 1:1 3:1 10:1 0.3:1 1:1 3:1 10:1
E:T E:T
Day 0 Day 5 Day 20 Day 0 Day 5 Day 20
1) Approximate illustration, for exact underlying clinical data, see Alici et al., 2008
10Scalable technology platform
- Potential to target wide range of indications including both solid and blood cancers
Favourable conditions
✓ Minimal residual disease (MRD) situation, ✓ Antibody acting through antibody-dependent
enabling efficient NK-cell therapies cell-mediated cytotoxicity (ADCC)
Multiple myeloma Amyloidosis Glioblastoma Hepatocellular Non-small-cell Breast cancer Other cancers
carcinoma lung cancer
Platform
A cancer of the A plasma cell An aggressive brain The most common The most common Cancer that forms The technology
Multiple plasma cells, a type disorder closely cancer with limited type of primary liver type of lung cancer in the cells of the platform could
myeloma of white blood cell related to myeloma treatments and a cancer, occurs most with no available breast are one of potentially be
that normally and other blood high degree of often in people with treatment that the most common suitable for
Other cancer produces antibodies cancers with limited recurrence chronic liver cures the cancer cancers globally treatment of a wide
indications available treatment diseases range of other
cancers
Blood cancers Solid tumours
11Current status of clinical development in MM
Multiple myeloma Preclinical Phase I Phase II Phase III Approval
ACP-001
Mono therapy study Completed FIH Phase I/II
(consolidation)
ISA-HC-NK
Combination study Ongoing phase II study
(consolidation)
Ongoing preclinical
Smoldering studies
Ongoing preclinical
Elderly studies
12Very good safety profile, promising efficacy data
Safety Overall survival Progression free survival1)
▪ No SAEs
1
▪ Majority of AEs Grade 1 (mild) 0,9 1,00
▪ Majority of AEs unlikely to be related 0,8
▪ The most frequently reported AEs, 0,7 0,75
reported in two or more patients (n), 0,6
were: 0,5
OS
PFS
0,50
OS
0,4
▪ shingles (n=4)
0,3
▪ upper respiratory infection (n=4) 0,2
0,25
▪ lumbago (n=3) 0,1
▪ diarrhea (n=2) 0 0,00
0 1 2 3 4 5 6 0 1 2 3 4 5
▪ headache (n=2) Time (years) Time (years)
▪ paraesthesia (n=2)
100% OS after a median
follow-up time of 60 Median PFS 34 months
Serendipitous side effect/proof of efficacy
months
Easily treated
EHA 2020: #EP914 - Autologous NK-cell-based immunotherapy for maintenance treatment of multiple myeloma Hareth Nahi et al.
13 1) Progression free survival: the length of time during and after the treatment of a disease, that a patient lives with the disease but it does not get worseIncreased Granzyme B as a surrogate biomarker
Granzyme B Serum (blood plasma) Bone marrow
▪ A protein that is secreted 12 5
by active NK cells
10
▪ Induces apoptosis (cell
Granzyme B (pg/mL)
4
Granzyme B [npx]
P103
death) of target cells for 8 P105
NK cells 6
P1063
P107
▪ Measurable levels indicate 4 P110
2
that NK cells are active P111
2
1
▪ Observation in bone
marrow especially 0
pre
30 min
60 min
240 min
pre
30 min
60 min
240 min
pre
30 min
60 min
240 min
-2 weeks
2 weeks
4 weeks
0
important as this is where at diagnosis 4 weeks after
the tumour cells are st nd rd
3rd
3rd infusion
1 infusion 2 infusion 3 infusion
located
EHA 2020: #EP914 - Autologous NK-cell-based immunotherapy for maintenance treatment of multiple myeloma Hareth Nahi et al.
14Cell-mediated immune defence
- Antibody acting through antibody-dependent cell-mediated cytotoxicity
Illustration of antibody-dependent cellular cytotoxicity (ADCC) Comments to ADCC
Antibodies NK cell CD16 Cross-linking Tumour cells die ▪ ADCC is a mechanism of cell-
bind antigens Fc receptors of CD16 by apoptosis mediated immune defence
on the surface recognize cell- triggers whereby an effector cell of the
of target cells bound degranulation immune system actively lyses
antibodies into a lytic a target cell, whose
synapse membrane-surface antigens
have been bound by specific
antibodies
▪ ADCC requires an effector cell
which classically is known to be
natural killer (NK) cells that
typically interact with
immunoglobulin G (IgG)
antibodies
15Phase II combination trial ongoing
- First of its kind study in collaboration with Sanofi, Karolinska Institutet & Hospital
Phase II study (ISA-HC-NK) initiated in Q2 2021
Description ▪ XNK Therapeutics’ lead candidate in combination with
isatuximab (anti-CD38 monoclonal antibody - mAb) to:
– amplify tumour cell recognition and killing via ADCC
– decrease mAb-related side effects
▪ NK cells express low levels of CD38, implying that a
combination with anti-CD38 monoclonal antibodies could be
beneficial as the NK cells themselves will not be targeted
Patient ▪ 60 patients to be recruited at Karolinska University Hospital
population Huddinge
Primary ▪ Overall response rate (ORR) including minimal residual
endpoint disease (MRD)
▪ Time to progression / progression free survival (TTP / PFS)
Secondary ▪ Duration of response (DoR)
endpoint ▪ Overall survival (OS)
▪ Safety
▪ Evaluate the activity and function of PBMCs and bone
Exploratory marrow-derived mast cells (BMMC)
endpoint
▪ Evaluate serum cytokine and chemokine levels
EudraCT: 2020-000994-26
16 ClinicalTrials.gov: NCT04558931GMP production
- In-house GMP-lab currently under construction, enabling expanded production capacity
Production
▪ Current production at the production unit at Karolinska
Cancer Center (KCC) Vecura
▪ Specialized GMP-lab, including QC and R&D, under
construction enabling full control
‒ Located at Huddinge, Stockholm (Sweden), in close
proximity to leading research and clinical and
current production
‒ Production of initially 100 batches per year which,
could be expanded upon need
‒ Enables efficient planning of production in the US
for future clinical studies
▪ Relatively low productions costs due to streamlined
production process and no gene modification of NK cells
Zahra Rajabkhani, Scientist from XNK Therapeutics
17Company highlights
1. Built on world-leading research on NK cells at Karolinska Institutet in Stockholm
A unique, proprietary autologous NK-cell based platform with tangible
2. development potential
The platform has ideal properties for targeting cancer across a wide range of
3. indications in mono- and combination therapy
First-in-human phase I/II study showing very good safety data and promising
4. efficacy data for the leading investigational drug product
Phase II study ongoing in patients with Multiple myeloma in combination with
5. Sanofi’s anti-CD38 antibody Sarclisa (isatuximab)
A potential USD multi-billion white space market opportunity in the US and in
6. Multiple myeloma alone
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