NASDAQ: PAND FEBRUARY 2021
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NASDAQ: PAND FEBRUARY 2021
Forward-Looking Statements and Disclaimers
This presentation contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 that involve substantial risks and
uncertainties, including statements regarding the development status of the Company’s product candidates and the timing of availability of clinical trial data. All
statements, other than statements of historical facts, contained in this presentation, including statements regarding the Company’s strategy, future operations, future
financial position, prospects, plans and objectives of management, are forward-looking statements. The words “anticipate,” “believe,” “continue,” “could,” “estimate,”
“expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward-looking
statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements are based on management’s current
expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth
in, or implied by, such forward-looking statements. These risks and uncertainties include, but are not limited to, risks associated with Pandion’s ability to obtain and
maintain necessary approvals from the FDA and other regulatory authorities; initiate preclinical studies and clinical trials of its product candidates; advance its product
candidates in preclinical research and clinical trials; replicate in clinical trials positive results found in preclinical studies; advance the development of its product
candidates under the timelines it anticipates in current and future clinical trials; obtain, maintain or protect intellectual property rights related to its product candidates;
manage expenses; and raise the substantial additional capital needed to achieve its business objectives. For a discussion of other risks and uncertainties, and other
important factors, any of which could cause the Company’s actual results to differ from those contained in the forward-looking statements, see the “Risk Factors”
section, as well as discussions of potential risks, uncertainties and other important factors, in the Company’s most recent filings with the Securities and Exchange
Commission. In addition, the forward-looking statements included in this presentation represent the Company’s views as of the date hereof and should not be relied
upon as representing the Company’s views as of any date subsequent to the date hereof. The Company anticipates that subsequent events and developments will
cause the Company’s views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, the Company
specifically disclaims any obligation to do so.
This presentation also contains estimates and other statistical data made by independent parties and by us relating to market size and other data about our industry.
This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such data and estimates. In addition, projections,
assumptions and estimates of our future performance and the future performance of the markets in which we operate are necessarily subject to a high degree of
uncertainty and risk. Neither Pandion nor its affiliates, advisors or representatives makes any representation as to the accuracy or completeness of that data or
undertakes to update such data after the date of this presentation.
PANDION THERAPEUTICS 2
Now is the Time for an
Autoimmune Breakthrough
80+ autoimmune Most with inadequate therapy, or
diseases without dedicated treatment
Critical insights into the role of
Advances in immune
regulatory cells and inhibitory
system biology
receptors
Activating natural Potential to rebalance rather than
control nodes supress the immune system
1830’s – 1940’s 1940’s – 1990’s 1990’s – 2020’s Next Generation
Empiric Steroids & Anti-Cytokines & Precision
Therapy Anti-Metabolites Kinase Inhibitors Biologics
PANDION THERAPEUTICS 3
1 Targeting critical control nodes with precision medicines to
rebalance overactive immune systems
2 Modular pipeline designed by TALON platform with potential
to address a broad range of autoimmune diseases
Engineered proteins to Lead program PT101: an engineered IL-2 potently and
3
precisely control the selectively expanded regulatory T cells (Tregs) in Phase 1a
clinical trial; clinical trials in two indications planned for 2021
immune system
4 Soluble and tissue-tethered PD-1 agonists designed to
control overactive immune cells, in preclinical development
5 Experienced leadership team with track record of execution
from discovery to marketing authorization
PANDION THERAPEUTICS 4
Pandion’s Modular TALON Drug Design Platform
Therapeutic Autoimmune reguLatOry proteiN
Systemically-Acting Tissue-Tethered
Effector module
acts at key control nodes
in the immune system
Antibody backbones
confer desired
drug-like properties
Tissue-tether module
imparts tissue selectivity
PANDION THERAPEUTICS 5
Modular Pipeline Targeting Underserved Autoimmune Diseases at
Site of Manifestation
Effector Candidate Location Discovery Preclinical Phase 1 Phase 2
Ulcerative Colitis
PT101
IL-2 Mutein Systemically-Acting
Systemic Lupus Erythematosus Expected
2021 milestones
PT002
GI/Liver
• PT101 Phase 1b/2a
PT627 initiation in UC mid-2021
Systemically-Acting
PD-1 Agonist
PT001 • PT101 Phase 2 initiation in
GI/Liver SLE in 2H 2021
Discovery Tethers
• PT627 IND filing in 2022
Pancreas
Pancreas
• PT001 IND-enabling
Kidney studies start 1H 2021
Kidney
Skin
Skin
Discovery Effector
CD39
PANDION THERAPEUTICS 6
IL-2 Mutein for Regulatory T Cell (Treg) Expansion
A Compelling Opportunity in Autoimmune Diseases
PT101
• Phase 1a clinical trial completed
PT101 – Well-tolerated; no serious adverse events
– Showed potent and selective expansion of Tregs
IL-2 Mutein – No evidence of expansion of pro-inflammatory cells
Treg selective • Phase 1b/2a trial in UC planned to start mid-2021
• Phase 2 trial in SLE planned to start 2H 2021
• Granted US composition of matter patent through 2038
Fully human
Fc backbone
Tregs Critical to Immune Homeostasis
• Patients with Treg defects have profound autoimmunity
• Tregs prevent and treat inflammation in animals
Low-Dose IL-2 Clinical Data Validate Approach
• >50% response rates in biologic-experienced moderate-to-severe
UC treated with low-dose IL-2
• Low-dose IL-2 clinical trials suggest patients with SLE achieve
disease control following 12-24 weeks of treatment
UC = ulcerative colitis
SLE = systemic lupus erythematosus PANDION THERAPEUTICS 7
Tregs Play a Key Role in Immune Homeostasis
Tregs Regulate
Activated Immune Cells
APCs • Regulate multiple immune cells
• Involved in tissue repair and regeneration
Tconv
• Critical for self-tolerance
– Defects cause multi-organ inflammation
Treg
– Dysfunction associated with IBD, SLE, MS,
T1D, other diseases
NK Cells
• Multiple third-party clinical trials suggest
Treg expansion with IL-2 can benefit
multiple autoimmune diseases
B Cells
PANDION THERAPEUTICS 8
Low Dose IL-2 as a Strategy for Activating Tregs
High Dose IL-2 Low Dose IL-2 • IL-2 critical growth factor for all T cells
• Tregs have high sensitivity for IL-2 due to
constitutive expression of IL-2Rαβγ trimer
IL-2Rαβγ • Low-dose IL-2 treatment has shown clinical
IL-2Rβγ Trimer
Dimer benefit in multiple autoimmune diseases
Tconv or Treg
Cellular Activation (%)
NK Cells
Pro-inflammatory Anti-inflammatory
for oncology for autoimmunity
High IL-2 concentrations Low IL-2 concentrations
activate Tconv and NK cells selectively activate Tregs
Wild-type IL-2 Concentration
PANDION THERAPEUTICS 9
Low Dose IL-2* Data Support PT101 Mechanism in UC
Low Dose IL-2 Expanded Tregs & Showed Promise in UC
Independent published data from Scott Snapper
Supports PT101 mechanism Dose A Dose B Dose C
Low dose IL-2 achieved >50% clinical
response rate in Dose B # of Patients 4 17 5
Aldesleukin Dose
Shows need for selectivity 0.3 1.0 1.5
106 IU/m2/d**
Narrow window before loss of Treg
selectivity and Tconv activation
≥2x Treg Expansion*** 100% and
50% 100%
% of pts Tconv activation
Low dose IL-2 not a solution for UC
Daily subcutaneous dosing; potential for
severe dose-limiting toxicities Clinical Response Rate
25% 52.9% 0%
week 8
Clinical Remission Rate
0% 23.5% 0%
week 8
*Aldesleukin
**millions of international units per meter squared per day
***achieved at least once during treatment vs baseline
Source: adapted from third party, Allegretti, et al, DDW May 5
PANDION THERAPEUTICS 10
2020, Abstract #1026Low Dose IL-2 Data Support PT101 Mechanism in SLE
Treatment Follow-up
80
Supports PT101 mechanism in SLE 60
Clinical benefit demonstrated in
SRI-4 (%)
multiple low-dose IL-2 clinical trials in
40
SLE, Sjogren's and lupus nephritis
Expansion of Tregs associated with 20
Low-dose IL-2 (n=29)
clinical benefit Placebo (n=30)
Low-dose IL-2 clinical trials associated 0
1.5-2X Treg expansion in responders in 0 2 4 6 8 10 12 14 16 18 20 22 24
Time (week)
two separate clinical trials
Low dose IL-2 (1 million IU) achieved clinical
response in ~66% of patients with SLE vs. ~37%
(placebo) at week 24, as measured by SLE
responder index-4 (SRI-4)
Subjects were dosed with recombinant human IL-2 (SL Pharm) every
other day for two weeks, followed by a two-week break through 12 weeks
Source: He, et al, Ann Rheum Dis 2019;0:1-9.
PANDION THERAPEUTICS 11Optimization and Selection of PT101
1 Reduce IL-2Rβ Affinity 2 Increase IL-2Rα Affinity 3 Optimize Format
N88D Selectivity Fc Fusion
Start with best known Enhance with structure- Best TALON format
mutation for Treg selectivity based engineering for Treg selectivity
PT101 IL-2 Mutein
N88D
IL-2Rα
IL-2Rβ
IL-2Rγ
PANDION THERAPEUTICS 12PT101 Selectively Activates Tregs vs Tconv and NK Cells
PT101 is selective • PT101 selectively activates Tregs due to
PT101
for Tregs Activated constitutive expression of IL-2Rαβγ trimer
immune cells
• Immune cells with only IL-2Rβγ dimer are
IL-2Rβγ IL-2Rα not activated
IL-2Rβγ
PT101 activates and
expands Tregs
Tconv Treg
Cellular Activation (%)
NK Cells
Activated immune
PT101 Concentration
cells are attenuated
PANDION THERAPEUTICS 13PT101 Phase 1a Trial Design
Design
Phase 1a Single Ascending Dose Study Screening Follow-up Period
• Blinded; randomized design Baseline Treg / Tconv / NK at multiple time points
• Single site; dedicated Phase 1 unit
D-10 D1 D28
• 56 healthy volunteers across 7 cohorts
• 8 subjects per cohort (6 PT101 : 2 placebo)
Endpoints Dose Placebo 1 mg 3.5 mg 5 mg 7.5 mg 10 mg
Safety, Tolerability, and Mechanism # Subjects 14 6 12 12 6 6
• Safety and tolerability
• Pharmacokinetics
• Treg / Tconv / NK at multiple time points
*PK = pharmacokinetics; PD = pharmacodynamics PANDION THERAPEUTICS 14PT101 was Well Tolerated; No Serious AEs Observed
• No serious AEs, deaths, dose-limiting
toxicity, or early study discontinuation
• No clinically important changes in vital Placebo 1 mg 3.5 mg 5 mg 7.5 mg 10 mg
signs or ECGs (n=14) (n=6) (n=12) (n=12) (n=6) (n=6)
Number with
• All AEs were Grade 1 or 2, mild to 3 (21%) 2 (33%) 4 (33%) 4 (33%) 4 (67%) 4 (67%)
any AE (%)
moderate, and self-limited
• Most common AEs were related to injection site reactions
• Some subjects had a transient elevation • Self-limited skin reactions extending beyond injection site occurred in
in eosinophils that were self-limited, not some subjects at doses of ≥7.5 mg
considered adverse, and believed may • Mild Grade 1 dyspnea was reported in three subjects, with no physical
be related to PT101’s mechanism exam findings, no limitation in activity, and no requirement for treatment
• Grade 2 AEs were only observed in the 10 mg group
• Dose proportional exposure;
half-life ~20-28 hours
• No induction of anti-drug antibodies was
observed
AE= adverse event
PANDION THERAPEUTICS 15PT101 Expanded Total Tregs in Healthy Volunteers
Total Tregs Mean Maximum Expansion
5 5
Placebo
Placebo
4 4
Fold Change
Fold Change
1.0mg
1 mg
Single dose
3 3.5 mg
3.5mg 3
5 mg
5.0mg
2 2
7.5 mg
7.5mg
1 10 mg
10.0mg 1
0 0
1 8 15 22 29
Placebo 1 mg 3.5 mg 5 mg 7.5 mg 10 mg
Time (days)
PT101 expanded total Tregs with up to a mean maximum fold change of 3.6
≥2-fold total Treg expansion associated with clinical benefit in third-party clinical trials in multiple autoimmune diseases
Values are mean (SEM) fold change in absolute cell count over baseline
Baseline: mean of measurement on Days -10 and 1 pre-dose for each subject
Common datapoints for cohorts 1-7 are shown; data was also collected from cohorts 4-7 on Days 6, 10, 12, and 22 (not shown)
Mean maximum value calculated using all timepoints PANDION THERAPEUTICS 16PT101 Markedly Expanded the CD25bright Treg Subset
CD25bright Treg Subset Mean Maximum Expansion
100 100
Placebo
Placebo
Fold Change
75
Fold Change
1 mg
1.0mg 75
3.5mg
3.5 mg
50 50
5.0mg
5 mg
Single dose
7.5mg
7.5 mg
25 25
10mg
10 mg
0 0
1 8 15 22 29
Placebo 1 mg 3.5 mg 5 mg 7.5 mg 10 mg
Time (days)
PT101 expanded the CD25bright Treg subset with up to a mean maximum fold change of 72.5
It has been reported that CD25bright Tregs may be a more active subset of Tregs with enhanced immune regulatory function
Values are mean (SEM) fold change in absolute cell count over baseline
Baseline: mean of measurement on Days -10 and 1 pre-dose for each subject
Common datapoints for cohorts 1-7 are shown; data was also collected from cohorts 4-7 on Days 6, 10, 12, and 22 (not shown)
Mean maximum value calculated using all timepoints PANDION THERAPEUTICS 17Robust Treg Response Rate Observed with PT101
Total Treg Expansion Responder Analysis (% of Subjects per Dose)
Fold Placebo 1 mg 3.5 mg 5 mg 7.5 mg 10 mg
Change (n=14) (n=6) (n=12) (n=12) (n=6) (n=6)
2x or
7% 33% 83% 83% 100% 100%
greater
3x or
0% 0% 58% 75% 33% 50%
greater
4x or
0% 0% 24% 42% 33% 17%
greater
More than 80% of subjects achieved 2-fold or greater total Treg expansion at doses ≥3.5 mg
A significant proportion of subjects achieved 3 to 4-fold Treg expansion at doses of ≥3.5 mg
PANDION THERAPEUTICS 18PT101 Maintained Treg Selectivity Throughout Dose Range
NK Cells CD4 Tconv Cells CD8 T Cells
500 1500 800
Absolute Number (cells/ul)
Absolute Number (cells/ul)
Absolute Number (cells/ul)
95%tile Placebo
Placebo
95%tile
400 95%tile
600 1 mg
1mg
1000
300 3.5mg
3.5 mg
50%tile 400 50%tile
5 mg
5.0 mg
200
500
50%tile 200 7.5mg
7.5 mg
100
Single 10 mg
10.0 mg
dose
0 0 0
1 8 15 22 29 1 8 15 22 29 1 8 15 22 29
Time (days) Time (days) Time (days)
NK cells, CD4 Tconv cells, and CD8 T cells remained within normal range at all doses tested
Values are mean (SEM)
50%tile and 95%tile are derived from analysis of 129 subjects’ Day -10 screening samples in Cohorts 1-7
Common datapoints for cohorts 1-7 are shown; data was also collected from cohorts 4-7 on Days 6, 10, 12, and 22 (not shown)
PANDION THERAPEUTICS 19Phase 1a Top-Line Data Summary
• PT101 was well-tolerated; no serious adverse events observed
• PT101 selectively expanded total Tregs to levels exceeding those associated with
clinical benefit in third-party clinical trials of low-dose IL-2
– At doses 3.5 mg and above, >80% of subjects achieved 2-fold or greater Treg expansion
– Mean maximum total Tregs expanded up to 3.6-fold above baseline
– Mean maximum CD25bright subset of Tregs expanded up to 72.5-fold above baseline
– Treg expansion profile supports every four-week dosing
• PT101 was selective for Tregs; no evidence of expansion of NK cells or pro-
inflammatory conventional T cells at any dose level
• Expect to initiate Phase 1b/2a clinical trial in patients with ulcerative colitis in mid-2021
and a Phase 2 clinical trial in patients with systemic lupus erythematosus in 2H 2021
PANDION THERAPEUTICS 20Significant Potential for
IL-2 Mechanism in
Autoimmune Disease Low-dose IL-2 POC
Type 1 diabetes
Rheumatoid arthritis • Third-party low-dose IL-2
clinical trials have
Industry Pipeline Crohn’s disease consistently shown
Alopecia areata benefit across multiple
GVHD autoimmune diseases
Takayasu’s arteritis • Tested in >200 patients
Atopic dermatitis Behcet’s disease
UC SLE
Ankylosing spondylitis
~2 million Psoriasis
Autoimmune hepatitis
in US
Granulomatosis with polyangiitis
+ ~24 million
in US Sjogren’s syndrome
+ ~11 million
in US
UC = ulcerative colitis
SLE = systemic lupus erythematosus
GvHD = graft versus host disease PANDION THERAPEUTICS 21PD-1, a Broadly PD-1 is a critical inhibitory immune control node
Applicable Drug Target • Mutations in PD-1 pathway are associated with autoimmune-
for Autoimmunity like disease manifestations
• Checkpoint inhibitors in oncology induce immune-related
adverse events in patients
• PT627 for systemic autoimmune diseases
• PT001 for GI/liver autoimmune diseases
• SLE and Lupus Nephritis • Vitiligo
• Rheumatoid Arthritis • Psoriasis
• Alopecia • Type 1 Diabetes
• Multiple Sclerosis • Colitis
• Kidney Transplant Rejection • Autoimmune Hepatitis
PANDION THERAPEUTICS 22PD-1 Agonist Franchise
PT627 PT001
Systemic & Soluble GI/Liver Targeted
Expect to file IND in 2022 IND-enabling studies
expected 1H 2021
PD-1 agonist effector
Does not interfere with
PD-1/PD-L1 interaction
Fully human IgG1
backbone
FcR null
MAdCAM tissue tether
Localization to GI tract
Leaves α4β7/MAdCAM
interaction intact
PANDION THERAPEUTICS 23PT627 Treatment Delayed Disease Onset
and Progression in xeno-GvHD Study
PT627 treatment delayed disease progression
PT627 treatment delayed disease onset
(Day 55)
Vehicle PT627
Weekly dosing D10-72
100
End of dosing
Survival (%)
50
PT627
Vehicle
0
0 20 30 40 50 60 70 80 90
Days post-engraftment
xeno-GvHD = xenogeneic graft vs host disease model: human blood cells are
grafted into immunodeficient mice; grafted human immune cells react to the
host mouse tissue to cause multi-organ inflammation and rapid loss of life
n = 15 mice per group 24
PANDION THERAPEUTICSPT001 MAdCAM-tethered PD-1 Agonist Showed Compelling
PD and Survival Advantage in xeno-GvHD Study
Prolonged survival beyond dosing in xeno-GVHD model Human Immune
n = 15 mice per group Cells Still Present
Survival (%)
Weekly dosing D10-72
100 End of dosing
50
PT001 Treated
Survivor mice exhibited limited
inflammation, but still had
human T cells >5 weeks beyond
end of dosing
PT001
MAdCAM control
Vehicle
0
0 20 30 40 50 60 70 80 90
Days post-engraftment
PANDION THERAPEUTICS 25TALON Platform Programs Show Promise of
Localized Immune Modulation
Effector Skin:PD-1 Skin:CD39
• Prevented depigmentation in vitiligo
Tether animal model
• Attenuated contact hypersensitivity
in animal model
• Decreased skin inflammation in psoriasis
animal model (not shown)
PANDION THERAPEUTICS 26Corporate
PANDION THERAPEUTICSCorporate Overview
Expected Milestones
PT101 (IL-2 Mutein)
• Phase 1b/2a UC start (mid-2021)
• Phase 2 SLE start (2H 2021)
• Explore additional PT101 indications
PD-1 Agonist Franchise
• PT627 (systemic) – file IND (2022)
• PT001 (GI/liver-tethered) – start IND-enabling studies
(1H 2021)
TALON Platform
• Continued advancement of TALON platform programs,
Astellas collaboration
Cash
• $232.3M in cash and equivalents at 9/30/2020
PANDION THERAPEUTICS 28You can also read
