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ADC Therapeutics SA Late Stage Oncology

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June 9, 2020 04:51 AM GMT
MORGAN STANLEY & CO. LLC
ADC Therapeutics SA | North America
Matthew Harrison
Late Stage Oncology Assets At
An Attractive Price; Initiate at
Overweight
Stock Rating
Overweight
Industry View
In-Line
Price Target
$53.00
We see ADC's two late stage pipeline assets which are in
pivotal studies for DLBCL and HL as having a high probability
of success and achieving >$1B in peak sales. Coupled with a
strong early stage pipeline and the validated PBD-based ADC
platform, significant upside opportunity remains.
Late stage opportunity with strong pipeline; We initiate at OW with a $53 PT:
ADC Therapeutics is developing a late stage oncology pipeline of drugs called
antibody drug conjugates (ADC). These are drugs which use the targeting power
of antibodies to more precisely deliver a highly toxic chemotherapeutic payload
to the cancer cells instead of the entire body. While ADCs are not a new
technology, ADC Therapeutics has been able to use a more toxic payload to
potentially deliver higher efficacy (Pyrrolobenzodiazepine or PBD). ADC's lead
assets are Loncastuximab Tesirine (Lonca) for late line DLBCL and Camidanlumab
Tesirine (Cami) for last line Hodgkin's lymphoma (HL). Together we believe these
assets can start generating revenues in 2021 and 2022, respectively with a peak
opportunity >$1B.
Lonca represents >$800M opportunity with real potential upside in early-stage
combination therapy: Lonca has demonstrated strong data in DLBCL (46% ORR,
20% CR) as well as FL (79% ORR, 64% CR). Importantly, the DLBCL data was
generated in tough-to-treat patients excluded in competitor trials, providing a
significant source of differentiation. Further, initial combination work with
ibrutinib has demonstrated a compelling signal in earlier stage DLBCL (77% ORR,
62% CR) offering a clear path to label expansion. We see a high probability of
approval in 2021 based on a 2H20 filing and model ~$580M in DLBCL sales by
2025E with an additional $200M in FL. Label expansion into earlier line of
therapy represent upside to our model.
Cami represents a ~$200M opportunity in HL, but solid tumors could be much
bigger: Cami is a highly potent agent for last line HL patients demonstrating an
ORR >80%. However, ~5% of patients had a serious side-effect of Guillain–Barré
syndrome (GBS). While early monitoring and effective intervention can help
these patients recover, Cami is likely to be restricted to last-line patients who
have failed other available therapies. Importantly, no solid tumor patients have
experienced GBS and solid tumors represent significant potential upside to our
EQUITY ANALYST
Matthew.Harrison@morganstanley.com
+1 212 761-8055
Zhen Zeng, Ph.D.
RESEARCH ASSOCIATE
Zhen.Zeng@morganstanley.com
+1 +1-212-761-2745
Connor Meehan
RESEARCH ASSOCIATE
Connor.Meehan@morganstanley.com
+1 212 761-8266
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ADC Therapeutics SA ( ADCT.N, ADCT US )
Biotechnology / United States of America
Stock Rating
Industry View
Price target
Shr price, close (Jun 8, 2020)
Mkt cap, curr (mm)
52-Week Range
Overweight
In-Line
$53.00
$35.25
$1,995
$37.98-28.50
Fiscal Year Ending
12/19 12/20e 12/21e 12/22e
ModelWare EPS ($)
Prior ModelWare EPS
($)
P/E
EPS ($)§
Div yld (%)
(2.34)
-
(2.94)
-
(2.44)
-
(2.18)
-
NM
-
NM
-
NM
-
NM
-
Unless otherwise noted, all metrics are based on Morgan Stanley ModelWare
framework
§ = Consensus data is provided by Thomson Reuters Estimates
e = Morgan Stanley Research estimates
QUARTERLY MODELWARE EPS ($)
2020e
2020e
Quarter
2019
Prior Current
Q1
(0.85)
Q2
(0.76)
Q3
(0.68)
Q4
(0.67)
2021e
Prior
-
2021e
Current
-
e = Morgan Stanley Research estimates
Morgan Stanley does and seeks to do business with
companies covered in Morgan Stanley Research. As a
result, investors should be aware that the firm may have a
conflict of interest that could affect the objectivity of
Morgan Stanley Research. Investors should consider
Morgan Stanley Research as only a single factor in making
their investment decision.
For analyst certification and other important disclosures,
refer to the Disclosure Section, located at the end of this
report.
1
~$200M last line HL forecast. We expect pivotal data in 1H21.
Path to commercialization to drive upside: While emerging data from Lonca in
combination with ibrutinib as well as confirmation of the durability of response
of Lonca in late-stage DLBCL represent near-to-mid term catalysts, we believe
the path toward commercialization and the launch of Lonca in DLBCL represents
the most significant catalyst for ADCT. With two late-stage, high differentiated
ADC programs, ADCT remains attractively valued versus peer ADC companies
with valuations of $5-10B. We continue to see significant upside for ADCT as the
pipeline matures.
2
Investment Summary
We are initiating coverage of ADC Therapeutics with an OW rating and a $53 price target.
The company is focused on developing potent anti-cancer therapeutics known as
antibody-drug conjugates (ADCs), which combine the targeted nature of antibody
therapies with potent, cell-killing agents. The late stage pipeline consists of two assets,
Lonca and Cami, both of which have potential to positively disrupt the oncology market.
Further, management is advancing a series of earlier-stage assets that represent
significant pipeline optionality in both liquid and solid tumor indications.
Exhibit 1: Late-stage Pipeline Opportunity
Source: Morgan Stanley Research, Company Reports; *after 25% interest to Genmab
Lonca may be the next drug of choice in late line DLBCL, and has potential for
expansion into earlier lines: Loncastuximab Tesirine, or Lonca, is ADC's lead asset, and
the drug is currently engaged in a pivotal PhII clinical trial, with potential to be approved
in 3L+ DLBCL in 2021. The drug has demonstrated comparable efficacy to competitive
agents, but is being studied in a much sicker population, suggesting to us differentiated
efficacy. As part of the commercialization strategy, management has expressed interest
in broadening patient access to Lonca by evaluating the drug in earlier lines of therapy.
To this end, Lonca has demonstrated strong efficacy in earlier lines of therapy in
combination with ibrutinib.
3
Exhibit 2: Lonca Efficacy Across Key Tumor Types
Source: Company reports
Dramatic efficacy for Cami provides positive risk/benefit in late-line patients:
Camidanlumab Tesirine, or Cami, is the second of ADCT's late-stage compounds in
development. The asset demonstrated significant efficacy in a PhI trial of R/R HL
patients, and is now being evaluated in a Pivotal PhII trial, with topline data expected in
1H21. Despite efficacy, safety has been an important consideration. There have been
several cases of Guillain–Barré Syndrome (GBS) across the PhI and PhII trials, which is a
potentially debilitating adverse event of special interest. Management has been
transparent regarding discussions with FDA, and GBS case rates have remained
relatively stable across trials, which is encouraging. With a clearly defined risk/benefit
profile, Cami is likely to have a future as a treatment for patients with last line HL.
Beyond HL, the drug is also being considered as a potential treatment for solid tumors.
Early stage pipeline is broad and represents optionality: ADC Therapeutics is advancing
several early stage assets across both liquid and solid tumor indications. ADCT-602, in
PhI/II development, is for the treatment of R/R B-cell Acute lymphoblastic leukemia
(ALL). ADCT-601 is the first pipeline asset intended exclusively for solid tumors, and
dose escalation has been completed. In preclinical models, ADCT-601 demonstrated
greater potency compared to a competitive agent in development by a competitor that
targets the same tumor antigen (AXL). Other early stage solid tumor-targeting assets
include ADCT-901 and ADCT-701, both of which with INDs planned for this year. Though
none of these assets are ascribed explicit value at present, maturing data may justify
including them in ADCT's valuation over time.
4
Exhibit 3: ADC Pipeline
Source: Company data, Morgan Stanley Research
Near term catalysts represent potential upside: The remainder for 2020 and 2021 are
likely to be critical years for ADC Therapeutics. With a BLA for Lonca in 3L+ DLBCL
planned in 2H20, potential approval in 2021, along with a key readout from Cami in 2L
HL expected at ASH in December 2020, ADC is primed for recognition by the investment
community. Efforts are also ongoing to expand growth prospects into the future:
management plans to initiate an additional pivotal PhII trial for Lonca in FL in 4Q20, and
development continues on the early stage pipeline.
Exhibit 4: ADC Therapeutics Aggregate Peak Sales Estimate ($M,
MSe)
Exhibit 5: ADC Therapeutics Target Selection
Source: Morgan Stanley Research
Source: Company Data
5
Exhibit 6: Upcoming ADC Therapeutics Catalysts
Source: Company Data
6
H
Risk Reward – ADC Therapeutics SA (ADCT.N)
Lonca in DLBCL/FL and Cami in HL drives risk reward
OVERWEIGHT THESIS
PRICE TARGET $53.00
Our $53 price target includes ~$1.3B in risk adjusted peak revenues by 2030E. We derive our
price target from a discounted cash flow (DCF) analysis that uses a discount rate of 10% and
a 0% terminal growth rate. The revenue drivers in our model are risk-adjusted, with
contributions from Lonca in 3L+ DLBCL, R/R DLBCL, R/R FL, and from Cami in 2L HL.
▪ We are Overweight ADC and believe the
data from late stage product candidates
Lonca and Cami supports approval and
commercialization of both products. We see
peak sales of >$1B.
Lonca has demonstrated efficacy both as a
monotherapy, and in combination, in
patients with 3L+ DLBCL. Expansion into
R/R FL remains a key opportunity, with a
pivotal trial starting later in 2020.
Cami safety is of key focus, and has
induced GBS in some patients. We believe
positive feedback from FDA suggests the
drug has a future in HL, and potentially solid
tumors, if the drug can maintain a clearly
defined risk/benefit profile.
Early stage pipeline represents optionality,
spanning both validated and novel targets
▪
RISK REWARD CHART
USD
$154.00(+336.88%)
$154.00
(+336.88%)
(+336.88%)
160
120
▪
▪
80
$53.00(+50.35%)
$53.00
(+50.35%)
(+50.35%)
40
0
JUN '19
Key:
Risk Reward Themes
$35.25
Disruption:
Share Gain:
Positive
Positive
View descriptions of Risk Rewards Themes, here
DEC '19
Historical Stock Performance
JUN '20
Current Stock Price
JUN '21
$2.00(-94.33%)
$2.00
(-94.33%)
(-94.33%)
Price Target
Source: Thomson Reuters, Morgan Stanley Research
BULL CASE
$154.00
BASE CASE
$53.00
BEAR CASE
$2.00
DCF
DCF
Cash/Share
Lonca achieves increased penetration in 3L
DLBCL, with POS-adjusted peak sales of
~$1B in the U.S. and $250M in the EU by
2030. Lonca eventually becomes available in
R/R FL, with POS-adj. peak sales of ~$493M
in the U.S., and ~$58M in the EU by 2030.
Cami is commercialized by 2021, with POSadj. sales of ~$584M in the U.s., and ~$158M
in the EU.
Lonca achieves solid penetration in 3L
DLBCL, with POS-adjusted peak sales in this
indication of ~$ 650M in the U.S. and $165M
in the EU by 2030. Lonca eventually
becomes available in R/R FL, with POS-adj.
peak sales of ~$319M in the U.S., and ~$27M
in the EU by 2030. Cami is commercialized
by 2021, with POS-adj. sales of ~$136M in
the U.S., and ~$33M in the EU.
Assumes all programs fail and the company
is valued at cash
7
H
Risk Reward – ADC Therapeutics SA (ADCT.N)
KEY EARNINGS INPUTS
Drivers
2019
2020e
2021e
2022e
Peak Sales (MSe) ($, mm)
1,338
1,338
1,338
1,338
INVESTMENT DRIVERS
Lonca in 3L+ DLBCL
Lonca in R/R DLBCL
Lonca in R/R FL
Cami in R/R HL
GLOBAL REVENUE EXPOSURE
20-30% UK
60-70% North America
Source: Morgan Stanley Research Estimate
View explanation of regional hierarchies, here
RISKS TO PT/RATING
MS ESTIMATES VS. CONSENSUS
RISKS TO UPSIDE
FY Dec 2020e
Lonca performs well in combination with
ibrutinib in earlier lines of therapy.
Lonca FL study provides registration data in
the mid-term and is approved
Cami demonstrates a strong signal in solid
tumors
RISKS TO DOWNSIDE
Lonca experiences a difficult launch and
underperforms expectations
GBS cases increase with Cami resulting in
termination of the trial
Lonca fails in FL or early stage DLBCL
combinations
Note: There are not sufficient brokers supplying
EPS
($)
Note: There are not sufficient brokers supplying
2.2%
HF Sector Net Exposure
19.6x
Source: Morgan Stanley Prime Brokerage. Includes
certain hedge fund exposures held with MSPB.
Information may be inconsistent with or may not reflect
broader market trends. Long/Short Ratio = Long
Exposure / Short exposure. Sector % of Total Net
Exposure = (For a particular sector: Long Exposure Short Exposure) / (Across all sectors: Long Exposure –
Short Exposure).
consensus data for this metric
(2.94)
consensus data for this metric
(193)
Net income
Note: There are not sufficient brokers supplying
($, mm)
consensus data for this metric
OWNERSHIP POSITIONING
HF Sector Long/Short Ratio
(194)
EBIT
($, mm)
Sales /
Revenue
($, mm)
3
Note: There are not sufficient brokers supplying
consensus data for this metric
Mean
Morgan Stanley Estimates
Source: Thomson Reuters, Morgan Stanley Research
8
Valuation
Exhibit 7: DCF Drives Valuation
Source: Company Data, Morgan Stanley Research Estimates
Our $53 price target includes ~$1.3B in risk adjusted peak revenues by 2030E. We derive
our price target from a discounted cash flow (DCF) analysis that uses a discount rate of
10% and a 0% terminal growth rate.
Valuation Methodology: We prefer the use of a DCF analysis to value biotechnology
companies. We believe a DCF fully captures both the upfront investment period as well
as the longer-term earnings potential of ADC Therapeutics' pipeline assets. While
investors do look at biotechnology on a multiples basis (P/E), we prefer a DCF as it is
more rigorous and requires more explicit assumptions about the long-term prospects of
a company.
Discount Rate: We utilize a 10% discount rate for ADC Therapeutics. In our coverage, we
utilize a 10% discount rate for all commercial companies, or those with pivotal data, a
12.5% rate for companies with complete randomized PhII data, and a 15% rate for all
development stage companies.
Terminal Growth Rate: We model explicit revenues through 2030E and assume a 0%
terminal growth rate from 2031E onwards.
Revenue: We include risk-adjusted revenues in our valuation. We explicitly model
revenues from Loncastuximab Tesirine (ADCT-402) and Camidanlumab Tesirine (ADCT302). We model peak probability of success-adjusted Lonca sales attributable to DLBCL
in the U.S. and EU at ~$816M by 2030, with an 85% probability of success (POS). In FL,
we model peak U.S. and EU Lonca sales at ~$346M by 2030, with a 50% POS. We model
peak POS-adjusted U.S. and EU Cami sales in HL at ~$170M by 2030, with a POS of
50%.
Economics: Patents for Lonca are co-owned with MedImmune, though ADC
Therapeutics has been granted an exclusive license to produce and sell the drug
globally, with all revenues attributable to ADC. For Cami, ADC Therapeutics has been
granted an exclusive license from Genmab to produce and sell the product globally.
25% of revenues associated with Cami will be attributable to Genmab, with the
remaining 75% to ADC Therapeutics.
COGS: We project COGS associated with Lonca to be 12% of product sales at launch
(2021), eventually decreasing to 5% by 2024 as a result of production efficiencies. We
estimate COGS associated with Cami to be 35% of product sales at launch (late-2021),
eventually decreasing to 28% by 2023.
9
Operating Expenses: We project total R&D expense of ~$152M in 2020e, ~$175M in
2021e, and ~$200M in 2022e, eventually stabilizing at 5% Y/Y growth in periods
thereafter.
Key Risks To Our Price Target Include: 1) Launch versus experienced large pharma peers
may be challenging; 2) Cami GBS case rate my increase, diminishing likelihood of success
for the drug; 3) Candidates may fail in label expansion studies.
10
Debate 1: Can Lonca Disrupt the Competitive DLBCL Market?
Overview: Compared with other last-line therapeutic options for DLBCL patients,
Lonca monotherapy has demonstrated significant efficacy with a tolerable sideeffect profile. Importantly, the favorable safety profile provides extensive
opportunities for use in combination, and suggests an opportunity for use in
earlier lines of therapy.
Street's take: Lonca, if approved, may provide a meaningful alternative for 3L+
DLBCL patients seeking a therapeutic with a more manageable safety profile than
Polivy, and a more convenient and cost-effective treatment than CAR-T. While
investors do see late-line DLBCL as a competitive environment, they understand
the differentiation in patients tested with Lonca.
Our take: In the last line/3L+ setting, Lonca monotherapy is likely to rapidly take
substantial market share, especially in the patient population excluded by other
therapeutic options. In combination, Lonca is likely to take additional share in this
broadened patient population, beginning with R/R DLBCL.
Introduction to ADCs
ADC Therapeutics' product pipeline is defined by antibody-drug conjugate technology,
which combines a monoclonal antibody to a cytotoxic payload, using a linker. These are
referred to as ADCs. Specifically, when administered to a patient intravenously, the drug
flows through the bloodstream, binds to a specific epitope on a target cell, leading to
internalization, cleavage of the linker, and subsequent release of the payload within a
cell’s cytoplasm. Release of this agent into a cell’s cytoplasm is often followed by cell
death. ADCs have demonstrated promise as anti-cancer therapeutics due to their
targeted nature and potent cell-killing capabilities. Further, the cytotoxicity associated
with ADCs provides a broader therapeutic window versus traditional chemotherapies(1).
The targeted potency of ADCs, though, does come at a price. Due to the cytotoxic
properties associated with the payload, ADCs can potentially be associated with greater
toxicity and negative side effects when compared to traditional 'n aked' antibodies, unless
dosing is managed well. ADCs may induce toxicity in a variety of ways – this can occur
when the linker is cleaved early, or if the antibody is non-selective. Common side effects
associated with ADCs are ocular toxicity, thrombocytopenia, and gastrointestinal (GI)
events including nausea, vomiting and diarrhea, neutropenia, and peripheral neuropathy.
When assessing an ADC as a product candidate, an evaluator must focus on both
efficacy and toxicity. Compared to other cancer-treatments, ADCs may be competitively
required to achieve greater response rates, especially if the drug’s safety profile is
unfavorable compared to marketed products. As a result, across the entire class of
(2)
11
drugs, toxicity is a key focus for patients, clinicians, and investors alike(2).
Anatomy of ADCs – Three Key Variables
The components of an ADC are key drivers of efficacy and toxicity, and optimization of
the antibody, linker, and payload combination is critical for developing commercial
drugs. A brief explanation of each of these elements can be found below:
Monoclonal Antibody (mAb) - Allows for the drug to target certain cells
selectively. Based on the variable (Fab) region, the mAb will bind with a specific
target cell. The target antigen will preferably be over-expressed on tumor cells,
thereby maximizing on-tumor effects.
Linker - Connects the cytotoxic payload to the monoclonal antibody. Linkers can be
either cleavable or noncleavable. ADCs with cleavable linkers have shown higher
efficacy than those with non cleavable linkers, though at the expense of reduced
stability in plasma, potentially leading to unintended side effects. This relationship
is reversed with noncleavable linkers, which require the entire conjugate molecule
to be internalized within a lysosome in order for the payload be released. This may
reduce efficacy, but be beneficial to overall toxicity. An ideal linker would have
stability in plasma, followed by efficient release once internalized by a target cell.
Cytotoxic Payload - Induces cell death. There are two key types of payloads, also
known as warheads – both promoting anti-tumor activity in different ways. First,
there are those that target tubulin and interfere with cell division. Second, there are
types of warheads that bind to and damage the DNA in a cell’s nucleus, blocking
cell division. Potent cytotoxicity is critical, because often only very few molecules
are affixed to a specific ADC(3).
ADCT Therapeutics' Approach
ADC Therapeutics' assets utilize a next-generation pyrrolobenzodiazepine (PBD)
cytotoxic payload, known as SG3199, for which management has secured proprietary
rights of use through an agreement with MedImmune. The PBD warhead, which is
affixed using a cathepsin-cleavable linker, induces cell death through a distinctly
different means than other marketed ADC products. That is, when introduced into a
cancer cell's cytoplasm, the PBD warhead creates cross-links in a cell's DNA without
disrupting the helical shape, leading to evasion of the cell's natural DNA-repair
mechanism. In preclinical models, this approach has achieved greater levels of potency
and less off-target toxicity (versus first generation PBD warheads).
The DLBCL Market
Diffuse Large B-Cell Lymphoma, or DLBCL, is a relatively common subtype of nonHodgkin lymphoma (NHL). DLBCL is typically an aggressive cancer that propagates
quickly, and is a result of malignant B-lymphocytes, which are a type of white blood cell.
The cancer may originate in the lymph nodes, which contain lymphocytes, or be
extranodal, where the cancer forms in the gastrointestinal tract, breast, brain, or other
organ in a patient's body. Although DLBCL is often aggressive, recent developments
have improved prognoses across all stages of diagnosis(4).
12
In particular, at the time of diagnosis, 24% of DLBCL cases are Stage I, 19% are Stage II,
17% are Stage III, and 34% are Stage IV (5% unknown staging). As with most cancers,
survival rates begin to decline as one moves along the staging continuum. Five year
relative survival rates for patients diagnosed with Stage I cancer are 73.3%, 72.7% at
Stage II, 63.7% at Stage III, 52.7% at Stage IV, and 57.7% for patients diagnosed with an
unknown stage.
DLBCL Treatment Paradigm
There remains a need for innovative therapeutics in the DLBCL market, especially for
patients whose cancers are later-stage at the time of diagnosis, and for those who
eventually become refractory to the standard of care (SoC). Generally, the first line of
treatment for a DLBCL patient is the R-CHOP chemoimmunotherapy regimen, which
includes rituximab (an anti-CD20 antibody), three chemotherapeutic agents
(cyclophosphamide, doxorubicin hydrochloride, and vincristine), and a steroid
(prednisone). Alternatively, the R-EPOCH regimen may be used, which involves adding
another chemotherapeutic agent (etoposide) to the R-CHOP regimen (5).
R-CHOP is an effective treatment for newly diagnosed DLBCL patients with more than
50% of patients being cured. However, between 40-50% of patients treated with the
regimen end up becoming refractory, requiring further treatment. After becoming
refractory to first line treatment, eligible patients may receive a stem cell transplant
(SCT) and high dose chemotherapy, and patients who progress further may be eligible
for treatment with novel therapies such as blinatumomab (an anti-CD3xCD19 bispecific
antibody), or polatuzumab vedotin (an anti-CD79b ADC). As patients move into third-tolast line therapy, CAR-T therapies may also be available. It is worth noting that there are
many more available therapies for DLBCL patients, the use of which is largely
dependent on a patient's transplant eligibility, disease sub-type, and line of treatment(6).
Loncastuximab Tesirine
The Warhead
ADC Therapeutics' lead program is the development of Loncastuximab Tesirine ("Lonca")
in patients with DLBCL. Lonca is a antibody drug conjugate; an anti-CD19 antibody
affixed to a next-generation PBD warhead with a distinct mechanism of action. As
mentioned briefly above, preclinical data suggest that these next-generation PBD
warheads exhibit less off-target toxicity than their first-generation counterparts, which
were originally investigated in the early 2000s. ADC's therapeutics utilize a dimer
warhead structure, which, after internalization by a cancer cell, binds with DNA without
disrupting the helical shape. Maintaining the structure of the DNA may help reduce the
likelihood of normal DNA repair mechanisms from hindering the effectiveness of the
drug. Once the warhead has bound with DNA in a cell, certain vital processes (such as
cellular replication) will be interrupted, eventually leading to cell death.
13
Exhibit 8: Lonca Mechanism of Action
Source: Company Data
The PBD dimer mechanism of action is distinct from other marketed ADCs, such as
Seattle Genetics' Adcetris (brentuximab vedotin) and Roche's Polivy (polatuzumab
vedotin) - both of which utilize a MMAE (monomethyl auristatin E) warhead. That is,
ADC's warheads have demonstrated significantly greater cytotoxic potency than those
used in other commercially-available ADCs. The image below depicts the in vitro potency
of common ADC warheads (in red), and traditional chemotherapeutic agents (in black),
as measured by IC50. It is worth noting that despite utilizing a more potent warhead,
ADCT's Lonca has an acceptable safety data in clinical trials, discussed further below.
Roche is covered by Mark Purcell
Exhibit 9: Common Warhead and Chemotherapeutic Potency
Source: Company Data
A common concern among targeted immunotherapies is the degree to which a cancer
cell expresses the antigen to which the therapeutic binds. The potency of ADC's PBD
warheads enables the drug to be effective in patients whose expression levels may be
low. Efficient cell killing is typically dependent on passing a certain threshold of
cytotoxic agent, which is the minimum number of molecules needed to achieve a cell
14
killing effect. ADC's highly potent warheads may lower this minimum threshold of
efficacy, which means the drug may still be efficacious in cancers whose antigen
expression is lower than usual. This characteristic may broaden the range of cancers
treatable by ADC's therapeutics, which has positive implications for both patients
seeking treatment, and ADC's total addressable market.
ADC's PBD-based ADCs operate by cross-linking separate strands of DNA, a process
known as interstrand cross-linking. This process, which is distinct from intrastrand crosslinking, allows the therapeutic-induced alterations to the DNA to persist for long periods
of time in the target cell, without distorting the helical structure (as discussed above).
This unique cross-linking method may lead to the subversion of DNA repair mechanisms
that might otherwise reduce the effectiveness of an anti-cancer therapeutic. Thus far,
few resistance mechanisms have been documented with regard to PBD warheads.
Clinical Development
Lonca targets CD19, which is a well established target found on normal, neoplastic B
cells, and follicular dendritic cells. The nature of the target makes it one of the most
reliable surface biomarkers for B cells. Lonca is currently engaged in a pivotal PhII
clinical trial, and is being evaluated in patients with relapsed or refractory (R/R) DLBCL.
The trial completed enrollment in September 2019, at which point 145 participants had
been enrolled. Patients are being treated with Lonca as a monotherapy, and, if
successful, the trial would support potential approval as a single in the 3L+ setting.
Thus far, the drug has demonstrated encouraging efficacy and a manageable safety
profile. In particular, activity has been observed in heavily pre-treated patients, some of
whom have received prior treatment with CD19-targeted therapies, or stem-cell
transplants.
Specifically, in PhII data as of October 14, 2019, DLBCL patients treated with Lonca
monotherapy achieved an ORR of 46% (66/145), with a CR of 20% (29/145), and a PR of
26% (37/145) - Presented at EHA, available here. These response rates are clinically
significant, especially due to the patients' prior treatment status, with a median of four
prior treatments. In particular, clinical responses were achieved in key sub-populations,
including patients with bulky disease, double-hit disease, triple-hit disease, elderly
patients, and those who did not respond to prior treatment. Bulky disease is when the
diameter of a patient's cancerous mass is ≥ 10cm. Patients whose cancer includes two or
three recurrent chromosome translocations are referred to as double and triple hit,
respectively, and the subtypes are typically associated with worse prognosis.
The most recent data from Lonca trials to date are summarized in the table below:
15
Exhibit 10: Initial Loncastuximab Tesirine Data in DLBCL, MCL, FL
Source: Company Data
The chart above also includes PhIb data from Lonca plus ibrutinib in DLBCL, in mantle
cell lymphoma (MCL) and follicular lymphoma (FL) patients, discussed further below.
In addition to monotherapy, as part of the commercialization strategy for Lonca,
management intends to seek approval for the drug in earlier lines of therapy, beyond
the 3L+/last line setting. In support of this effort, Lonca has demonstrated significant
efficacy when dosed in combination with ibrutinib (a commonly used BTK inhibitor for
treating other blood cancers). In preliminary data from the PhIb trial, Lonca plus
ibrutinib demonstrated an ORR of 77% (10/13), with a CR of 62% (8/13), and a PR of 15%
(2/13). Based on these results, management intends to bring Lonca into an additional
pivotal PhII trial as a post-marketing effort. The trial is likely to be in combination with
rituximab, a well-validated anti-CD20 antibody for the treatment of patients with NHL. If
successful, this pivotal PhII trial of Lonca + rituximab would support commercialization
of the drug in the 2L setting.
Further, management has indicated their interest in pursuing label expansions into other
cancer types beyond DLBCL, based on the preliminary data summarized in Exhibit 10
above. In particular, plans for follicular lymphoma (FL) are a key focus. Management
intends to start a pivotal PhII trial in indolent lymphoma in 4Q20. The trial is likely to
enroll ~85 patients, ~70 of whom will be FL patients. As depicted above, preliminary
results from Lonca in FL patients have been encouraging. Among 14 FL patients treated
with Lonca monotherapy as part of the PhIb trial, 64% (9/14) achieved a CR, and 14%
(2/14) achieved a PR, yielding an ORR of 79%. Importantly, patients had been heavily pretreated, with a median of five prior lines of therapy.
In summary, regulatory plans for Lonca are as follows:
Lonca Monotherapy in DLBCL (3L): File BLA in 2H20
Lonca + rituximab in R/R DLBCL (2L): Plans to initiate a Pivotal PhII trial in 2H20
Lonca in FL: Intend to initiate a Pivotal PhII in FL in 4Q20
Lonca in MCL: To be determined
16
Exhibit 11: Lonca Single Agent Duration of Response, Pivotal PhII DLBCL Trial
Source: Company Data
Durability has also been strong with Lonca. In the Kaplan-Meier diagrams above, DLBCL
patients that achieved complete responses in the ongoing pivotal PhII trial
demonstrated durable responses, given the heavy pretreatment status. Based on these
data, management intends to file a BLA in 2H20, with potential for approval in 3L+
DLBCL (monotherapy) in 2021.
Lonca Safety
In the Pivotal PhII DLBCL Lonca monotherapy trial, ~63% of patients (92/145)
experienced Grade ≥ 3 TEAEs. The most common Grade ≥ 3 TEAEs (>5% incidence) were
decreased neutrophil count (~23%, 34/145), increased gamma-glutamyltransferase
(~14%, 20/145), decreased platelet count (~14%, 20/145), and anemia (~10%, 14 /145). A
prior analysis revealed cases of hypercalcemia, increased alanine aminotransferase,
hypokalemia, and leukopenia, though at rates <5% in the 145-patient interim analysis.
Importantly, in the 145-patient analysis, 16.6% of patients (24/145) discontinued
treatment as a result of AEs that emerged during treatment. 9% of patients (13/145)
discontinued treatment as a result of AEs that arose as a result of treatment with
Lonca. These discontinuation data can interpreted as: ~54% of discontinuations (13/24)
were a result of treatment with Lonca. 7% of patients (10/145) in the original 145-patient
dataset had a dose reduction.
The safety data summarized above suggest that Lonca has a manageable safety profile
both as a monotherapy and in combination (no new safety signals were observed when
administered in combination with ibrutinib). This characterization, and safety in general, is
of the utmost importance when considering Lonca's commercial future. In late line
settings, the drug must have a favorable safety profile versus other novel 3L+ DLBCL
treatments (such as CAR-T). In the context of ADC's defined commercial strategy, in
order to be considered as a competitive early-line therapy, the drug must deliver
superior efficacy versus other approved treatments, while maintaining a relatively
manageable toxicity profile, or at least comparable to other treatments in the early
setting.
17
Exhibit 12: Interim Pivotal PhII Lonca DLBCL Safety Data, TEAEs Gr ≥3
Source: Company Data
Competition in DLBCL
As discussed above, the DLBCL treatment landscape is competitive. In order to gain
share, Lonca will need to demonstrate superiority (or comparability) to other late-line
DLBCL treatments, if commercialized first in the targeted 3L+ setting. In the late-line
DLBCL setting, and considering only currently-approved therapeutics, Lonca is likely to
be competing primarily for market share against Polivy, which is Roche's CD79b-directed
ADC (polatuzumab vedotin), and Kymriah or Yescarta, which are Novartis and Gilead's
CAR-T therapies, both approved for use in patients with R/R DLBCL.
Polivy is approved in combination with bendamustine (a chemotherapeutic agent) and
rituxumab (an anti-CD20 antibody) for use in R/R DLBCL patients that have received at
least two prior therapies (3L+). In confirmatory trials, in 45 patients treated with Polivy,
50% achieved a CR, and 13% achieved a PR, yielding an ORR of 63%. Though this
compares favorably to the 46%/20%/26% ORR/CR/PR demonstrated in 145 patients by
Lonca, especially given that Lonca patients had a median of 3 prior therapies versus 2
with Polivy. Patients treated with Polivy experienced ≥ Grade 3 AEs, in some cases, at
rates more than double that of patients treated with Lonca. In particular, 61% of
patients experienced neutropenia (vs. 23% for Lonca), 31% experienced
thrombocytopenia (vs. 14% for Lonca), and 24% experienced Anemia (vs. 10% for
Lonca)(7).
In addition, Polivy is approved only for use in combination with bendamustine, an agent
commonly associated with myelosuppression, which can lead to AEs such as anemia
(low red blood cell count), thrombocytopenia (low platelet count), leukopenia (low
white blood cell count), among other hematological abnormalities. More specifically, in
two confirmatory studies with NHL patients, treatment with bendamustine led to
≥ Grade 3 myelosuppression in 98% of patients(8).
Lonca may also provide an alternative to CAR-T therapies which are efficacious, but
come with significant side-effects and cost. In general, Chimeric Antigen Receptor (CAR)
T-cell therapy leverages the natural ability of the human immune system to recognize
and kill cancer cells. CARs are genetically-engineered cell surface receptors built to
equip a patient’s own T-cells with the ability to recognize and bind to antigens (cell
surface proteins) found on cancer cells. This process, which is approved for use by
DLBCL patients, involves genetically transferring the CAR gene directly into a patient’s
own T-cells. Ultimately, when infused back into the patient, the CAR enables T-cells to
(9)
18
effectively recognize and eliminate cancer cells(9).
At the time of publishing, the two approved CAR-T therapies are Kymriah (from Novartis,
covered by Mark Purcell), and Yescarta (from Gilead). These two therapies, in
confirmatory trials, have demonstrated ORR/CR/PRs of 50%/32%/18% and 72%/51%/21%,
respectively. Importantly, most CAR-T patients need to be hospitalized in the ICU for a
period of time after treatment due to the significant toxicity.
A full comparison of Lonca versus key competitive therapies is shown below:
Exhibit 13: Lonca vs. Competitive Approved Therapies
Source: Company Data, Kymriah Label, Yescarta Label, Polivy Label
In addition to currently approved late-line DLBCL treatments, there are series of
therapies in development from various competitor firms to ADC. Specifically, we
highlight 5F9 (magrolimab) from Gilead (originally Forty Seven, since acquired), MOR208
from MorphoSys (not covered), and ublituximab and ubralisib from TG Therapeutics
(not covered). Though it is early in clinical development for the aforementioned
competitors, we note that Lonca monotherapy data in DLBCL is competitive versus
these agents. We will also watch novel bi-specific antibodies which could compete in the
late-line DLBCL setting as well.
Exhibit 14: Lonca vs. Competitive Therapies In Development
Source: Company Data. *DLBCL patients only
19
The Lonca Market Model
Based on current timelines, with a BLA for the 3L+ setting planned in 2H20, we model
initial approval of Lonca in the U.S. and EU in 2021. Further, we model a 2L label
expansion, and approval in the relapsed or refractory (R/R) setting by 2024 in the U.S.
and EU. We do not currently model explicit entry into the 1L setting. At launch, we
estimate there to be ~6,800 eligible patients in the U.S., and ~6,000 in the EU. These
estimates include those who have failed induction therapy, failed SCT, and 3L+/last
resort patients. By 2024, with the entry into an earlier line of therapy, these figures
increase to ~12,800 eligible patients in the U.S., and ~12,000 in the EU. We model peak
U.S. Lonca DLBCL sales at ~$651M in 2030, and peak EU Lonca DLBCL sales at ~$164M
in 2030. These estimates are probability of success (POS) adjusted by 85% to account
for the inherent risk associated with drug development.
In addition to 2L/3L+ DLBCL, we model a label expansion of Lonca into FL by 2022 in the
U.S., and 2023 in the EU. We estimate the drug will be initially available in the 2L FL
setting. In the U.S., the 2L FL setting represents an ~8,000 patient addressable market
(by 2022), and in the EU, a ~5,500 patient market (by 2023). We model peak U.S. Lonca
FL sales at ~$319M in 2030, and peak EU Lonca FL sales at $27M in 2030. These
revenue estimates apply a more punitive POS-adjustment (50%) than the DLBCL model,
due to the earlier-stage nature of the FL program.
Generally, we do not expect an impact from patent cliffs until after our modeled
projection period (Present - 2030). ADC has both been granted and has pending
applications for a series of utility patents associated with Lonca that expire between
2031 and 2038. Specifically, ADCT has been granted utility patents for Lonca in the U.S.,
Europe, Japan, and China, and additional utility patents are pending in these regions.
Exhibit 15: Eligible Patient Count by Year Approved/Label Expansion,
MSe
Exhibit 16: Lonca Revenue Estimates, MSe
Source: Morgan Stanley Research
Source: Morgan Stanley Research
20
Debate 2: What Is the Market Potential of Cami?
Overview: In early clinical evaluations, Cami has demonstrated significant efficacy
in heavily pretreated HL patients, many of whom who have failed prior treatment
with other leading therapies for R/R disease. Despite cases of GBS, and the
resulting partial clinical hold, the drug likely has a future in last line cHL and
potentially solid tumors.
Street's take: Investors are keenly focused on Cami's safety profile, and whether
or not the asset has the potential to be approved. Most investors see Cami as a
$200-300M asset in last line HL.
Our take: If the asset continues to demonstrate a clearly defined risk/benefit
profile, Cami represents an opportunity for management to provide a potent
therapeutic for late-line HL patients. Given cases of GBS, the drug is likely to
remain relegated to later lines of therapy, but the solid tumor opportunity may
expand Cami's addressable market size and contribution to valuation, longer term.
Camidanlumab Tesirine
After Lonca, ADC's second key product in development is an ADC known as
Camidanlumab Tesirine, or 'Cami.' Similar to Lonca, Cami is equipped with ADC's
proprietary PBD-dimer warhead (SG3199), using the same linker technology. However,
the warhead is affixed to an anti-CD25 antibody, and is currently in development for the
treatment of R/R Hodgkin's Lymphoma (HL), NHL, and solid tumors.
Background of Hodgkin's Lymphoma
Hodgkin’s Lymphoma, or HL, is a cancer of the lymphatic system, and is subdivided into
classical HL (cHL) and nodular lymphocyte‐predominant HL (NLPHL). HL arises from
malignant post-germinal B-cells, which typically become surrounded by a series of
inflammatory immune cells, such as lymphocytes, eosinophils, neutrophils, histiocytes,
and plasma cells. The malignant B-cells are often a minority in the resulting tumor, and
the inflammatory immune cells surrounding them can be pathogenic. As a whole, these
cells are termed Hodgkin and Reed-Sternberg (HRS) cells. The presence of HRS cells is
ubiquitous in cases of HL. Of interest is cHL (>90% of cases), which, despite being more
common in younger patients, is seen in all age groups. The disease often presents itself
as a mass in a patients’ lymph node, or in the mediastinum, which is the area between
the sternum and spinal column (10).
CD25 is expressed by some Reed-Sternberg cells, and by most polyclonal T-cells, which
are often found adjacent to a Reed-Sternberg cell mass. CD25 is a clinically validated
target for therapies that block IL-2 receptor function and inhibit T-cell proliferation, and
21
is expressed across various hematological malignancies (such as B- and T-cell
lymphomas). These factors make CD25 a good target for treating patients with cHL(11).
Treatment Paradigm in cHL
First line therapy for patients with advanced cHL is typically a chemotherapy regimen of
adriamycin, bleomycin, vinblastine, dacarbazine (ABVD). Other chemo regimens include
BEACOPP and Stanford V. In addition to chemo, first line treatment of cHL may include
surgery, radiation therapy, and Adcetris, which is the only ADC approved in combination
with chemo in the first line setting.
Many patients with advanced cHL may experience relapsed or refractory (R/R) disease,
and will require additional treatment. Second line and third line treatment may include
additional regimens of high-dose chemotherapy, and, in eligible patients, autologous
hematopoietic stem cell transplantation (auto‐HSCT). Allogenic stem cell
transplantation may also be an option, though there is a risk of graft-vs-host disease
(GvHD). In addition to chemo and stem-cell transplantation, later lines of treatment may
include immunotherapy – such as checkpoint inhibition. Anti-PD-1/PD-L1 antibodies such
as nivolumab and pembrolizumab have been successful in treating some R/R cHL
patients (due to over expression of these antigens on the cells involved in the
pathogenesis of cHL).
Antibody-drug conjugates, such as Cami, have also risen to prevalence as potential
treatment options for patients with R/R or advanced cHL(12).
Development Progress
Though the drug is in development in multiple indications, Cami is in late-stage
development in classical Hodgkin's Lymphoma (cHL). Management is currently
evaluating Cami in a 100-patient pivotal PhII clinical trial. The trial includes patients who
have been diagnosed with R/R cHL, and are heavily pre-treated, requiring patients to
have failed at least three prior treatments (or two for HSCT-ineligible patients),
including brentuximab vedotin (marketed as Adcetris by Seattle Genetics), and a
checkpoint inhibitor, or stem cell transplant. As of April 2020, 47 of 100 patients had
been enrolled in the trial, and management plans to report pivotal data from this PhII
trial in 1H21. At present, however, the trial has been placed on partial clinical hold as a
result of an agreement with the FDA, discussed further below.
In early evaluations, Cami demonstrated significant efficacy in heavily pretreated cHL
patients. Enrollment in a 133-patient PhI trial including both R/R NHL (n=51) patients and
R/R HL (n=77) patients (among other disease types) has been completed, and initial data
has been disclosed. In the HL cohort, at the 45 μg/kg dose level (37/77), 48.6% of
patients achieved a CR (18/37), and 37.8% achieved a PR (14/37), yielding an ORR of
86.5%. Patients in this sub-population had a median of five prior lines of therapy,
suggesting that Cami has the potential to be efficacious in patients that have become
refractory or not responded to the current standard of care. Further, the ~87% ORR is
more than double that of commercially available late-line HL therapies. Despite
protocol adjustments based on discussions with FDA, 45 μg/kg remains the initial dose
level in the pivotal PhII study. Specifically, in the PhII trial, Cami is to be administered
intravenously at 45 μg/kg for 30 minutes for two cycles (each three weeks), followed by
30 μg/kg for subsequent cycles.
22
A summary of the PhI HL Cami data (n=77) can be found below:
Exhibit 17: Cami PhI HL Data, Preliminary (45 μg/kg)
Exhibit 18: Cami PhI HL Patient Characteristics
Source: Company Data
Source: Company Data
Full PhI Cami efficacy data is shown below, all dose levels included. 75/77 patients were
subjected to a post treatment efficacy assessment.
Exhibit 19: PhI Cami Efficacy Data, All Doses
Source: Company Data
The median duration of response (mDOR) in the PhI trial, across all dose levels, was 6.4
months. In patients that achieved a CR, the mDOR was 8.1 months, and 5.1 months for
patients that achieved a PR. In the 45 μg/kg dose cohort, the mDOR was 7.2 months for
patients that achieved a CR, and 5.6 months for patients that achieved a PR, and 6.6
months overall.
23
Exhibit 20: PhI Cami 45 μg/kg Median Duration of Response (4/14/19 Cutoff)
Source: Company Data
Interim data from the ongoing PhII HL trial has also been released. As of April 2020, 24
patients had been evaluated for responses. The preliminary analysis has showed an
ORR of 66.7% (16/24), with 16.7% of patients achieving a CR (4/24), and 50% of patients
achieving a PR (12/24). Though preliminary, these data are roughly consistent with PhI
results, as of first disease assessment. We note that the PhI data described above is the
complete dataset, and therefore differs from the figures below.
Exhibit 21: PhII and PhI Cami Efficacy Data Comparison (as of first data assessment)
Source: Company Data
A summary of key competitive cHL assets can be found below. As discussed above, Cami
has shown superior efficacy, though with certain TEAEs of special interest, discussed
further below:
Exhibit 22: Cami Data vs. Competitive Approved Agents
Source: Company Data; * Treated at or above 45 µg/kg, the initial dose in the pivotal PhII trial
24
Safety/Guillain–Barré Syndrome
While the maximum tolerated dose (MTD) was not reached as part of the PhI dose
escalation trial, 66.2% of HL patients (n=77) experienced a grade ≥ 3 TEAE. At the 45
μg/kg dose level (n=37), 67.6% of patients experienced a grade ≥ 3 TEAE. Full PhI safety
data are summarized in Exhibit 23 below, but key grade ≥ 3 TEAEs from the 45 μg/kg
cohort are as follows: gamma-glutamyltransferase increase (3/37, 8.1%), maculopapular
rash (8/37, 21.6%), alanine aminotransferase increase (3/37, 8.1%), and, of particular
interest, Guillain–Barré syndrome/polyradiculopathy (3/37, 8.1%).
Cami's safety profile has been a key topic of discussion due to multiple cases of
Guillain–Barré syndrome/polyradiculopathy ('GBS') arising in HL patients during both PhI
and PhII trials. GBS is a disorder that may be induced as a result of being treated with an
ADC. When a patient develops GBS, their immune system begins to attack their nerves, a
process which can eventually lead to paralysis. GBS is often considered a medial
emergency, and unless treated early, may drastically diminish a patient's likelihood of
survival. GBS is often characterized by muscle weakness, double vision, severe pain,
rapid heart rate, low/high blood pressure, and difficulty breathing, among other
symptoms. Treatment typically includes plasmapheresis and/or immunoglobulin
therapy. While symptoms typically subside within several weeks, full recovery after a
GBS event, if at all, is often prolonged, and may take years(13).
The rate at which GBS occurs in patients treated with Cami is of keen interest for both
investors seeking to evaluate Cami's future as a therapeutic, and for clinicians looking to
evaluate the drug's risk/benefit profile.
Exhibit 23: PhI Cami Data by Dose Level
Source: Company Data
Cases of GBS have occurred on multiple occasions in HL patients being treated with
Cami. In August/September 2017, ADC notified the FDA that two HL patients had been
diagnosed with GBS, and one with polyradiculopathy (a specific type of GBS), after being
treated Cami. Following this notification, the FDA instructed ADC to paused enrollment
in the trial, but allowed management to continue with dosing for patients that had not
experienced GBS as an adverse event. Based on discussions with FDA, management
broadened exclusion criteria and added routine neurological monitoring, among other
protocol modifications, and, in January 2018, was given clearance to proceed with
evaluation.
After being given permission from the FDA to proceed, in September 2018, two
additional HL patients were diagnosed with GBS. In this second instance, management
25
suspended enrollment in the PhI trial and performed a safety review, which was
subsequently submitted to the FDA. After reviewing the data, a Clinical Advisory Panel
reported a possible positive risk/benefit associated with Cami, and by October 2018,
management had been given permission to proceed. FDA had requested that
management both expand the PhI 30 μg/kg dose cohort by 10 HL patients, and consult
with the agency prior to selecting a dose level for the PhII trial. As of May 2019, both
GBS patients had achieved a CR, and were still alive.
As of March 2020, after progressing into the PhII stage of clinical development, two
additional patients were diagnosed with GBS. After an April 2020 meeting with FDA, the
PhII trial has been placed on a partial clinical hold, which prevents new patients from
being enrolled, though the regulatory agency has allowed management to continue
dosing in all patients currently enrolled.
An illustrative timeline of the events leading up to the partial clinical hold can be found
below:
Exhibit 24: Cami Clinical Development, GBS Timeline (Illustrative Only)
Source: Company Data, Morgan Stanley Research
At the time of publishing, management has not commented on the likelihood of any
further delay in the planned pivotal PhII readout in 1H21. Though a clinical hold is often
reason for scrutiny, we see opportunity for Cami despite the setback:
Prior communication between ADC and FDA would suggest the regulatory agency
has an interest in working with management to bring Cami to market, based on the
risk/benefit profile.
Despite the instances of GBS, the case rate (%) has remained relatively stable
across PhI (~8%, 3/37) and PhII (~4%, 2/47) trials.
It is believed that GBS is an indication-specific adverse event (for HL), as there have
been no cases of GBS observed in the >120 NHL patients that have been treated
with Cami.
Regarding the partial clinical hold that was instituted in April 2020, ADC submitted a
supplemental data package in May, whereby the FDA has 30 days to respond. As a
result, an update is to be expected in June 2020, or early July.
Indications Beyond HL
Management has been exploring the potential for Cami as a therapeutic in indications
outside of Hodgkin's Lymphoma. The drug is currently being evaluated as part of a PhIb
clinical trial as monotherapy in patients with advanced solid tumors by targeting Treg
26
cells, which are typically involved in suppressing/downregulating the immune system. By
diminishing the number of immunosuppresive Treg cells in the tumor microenvironment,
Cami may help a patient's immune system detect and destroy malignant solid tumor
cells. Cami has three attributes that may drive efficacy in the solid tumor setting:
Treg cell depletion to help diminish immune system evasion by cancer cells
The PBD warhead may contribute to cancer cell-killing through the bystander
effect
Immunogenic cell death may lead to an enhanced immune response
Exhibit 25: Proposed Cami Solid Tumor Method of Action
Source: Company Data
As of April 14, 2020, 34 patients have been treated with Cami. No DLTs have been
observed, while Grade ≥ 3 AEs was reported in 22 patients. The most common AEs
include anemia, rash, hypophosphatemia, and pulmonary embolism. Stable disease was
achieved in 4 patients among 27 with tumor response assessment. In paired biopsies
from 3 out of 6 patients in the PhIb trial, a significant increase in the ratio of T effector
cells (Teff) to Treg has been observed in the tumor and adjacent tissue after treatment
with Cami. More interim data from the ongoing PhIb trial of Cami in solid tumors is
expected at a medical conference (potentially ESMO) in 2H20. In order to enhance the
effects described above, management has also proposed, in the case of solid tumors,
combining Cami with an approved checkpoint inhibitor, such as pembrolizumab.
Preclinical Cami Solid Tumor Data
Prior to the initiation of the PhIb solid tumor trial, a similar ADC to Cami was evaluated
in a variety of mouse models to assess the drug's pre-clinical efficacy. Due to the
structure of the Cami antibody, the drug does not bind to murine (mouse) CD25, limiting
its relevance in generally accepted preclinical mouse models. As a result, the data
outlined below are from an ADC with a surrogate antibody (Sur301), which binds to
murine CD25, and is affixed to the same PBD warhead.
In vivo, as part of the MC38 mouse model, management observed a synergistic effect
27
between Sur301 and an anti-PD1 antibody, shown below. The combination of an antiPD1 antibody and Sur301 led to the sustained suppression of mean tumor volume, over
time.
Exhibit 26: Synergistic Effect of Sur301/anti-PD1 in the CD25 Negative MC38 Syngeneic Mouse
Model
Source: Company Data
Further, re-grafting of survivor mice with MC38 cancer cells led to continued survival,
and none of the subjects developed tumors as part of this second iteration of testing.
This observation suggests the inducement of immunological memory after treatment
with Sur301, which may lead to longer, more durable responses.
Exhibit 27: Re-Grafting of Surviving Mice, MC38 Model
Source: Company Data
The Cami Market Model
Based on the positive commentary on Cami to date, a planned pivotal PhII readout in
1H21, and management's expectation to file a BLA in 2021, we estimate the drug will be
first commercialized in the HL in the U.S. in 2022, followed by the EU later in 2022.
Based on Cami's safety profile, to begin, we model initial commercialization in the last
line HL setting, for patients receiving last resort treatment. We estimate this population
to be ~820 patients in the U.S. by 2021, and ~1,000 patients in the EU by 2022. We
model label expansion in the U.S. by 2023, eventually including R/R patients, and those
that failed induction therapy, summing to ~2,000 additional patients. In the EU, we
estimate this same incremental population to be ~2,400 patients by 2023.
28
Across both the U.S. and EU, we model peak Cami sales of ~$170M by 2030 in HL, and
do not include solid tumor estimates in our revenue projections. Due to the higher risk
associated with the asset, we apply a 50% probability of success adjustment to our
estimates. Importantly, we include a 25% haircut to the estimates to account for a
collaboration and license agreement that was originally struck between Genmab and
ADC in 2013. As with Lonca, though subject to the licensing agreement with Genmab,
there are multiple utility patents associated with Cami in a variety of geographies,
expiring between 2031 and 2039. As a result, we do not see a patent cliff as a significant
risk to Cami during our projection period (Present-2030).
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Debate 3: What Is the Next Upside Driver for ADCT?
Overview: ADC Therapeutics has a variety of product candidates in its pipeline
that, if successful, represent an opportunity to extend revenue streams beyond
the two lead programs. The most advanced candidates include two assets in the
clinical stage, ADCT-601 and ADCT-602, and two preclinical assets, ADCT-701 and
ADCT-901, for which INDs are expected within the year. Once ADC Therapeutics'
proprietary ADC platform is fully validated through the ongoing pivotal studies,
more product candidates may arise in the future.
Street's take: The pipeline beyond Lonca and Cami is not yet a primary focus for
investors. Initial data from ADCT-601 and ADCT-602 have been encouraging,
though explicit value is not ascribed to these assets.
Our take: We currently do not model any revenue from the product candidates
herein (ADCT-602, ADCT-601, ADCT-901, ADCT-701). As a result, ADCT's early
stage pipeline represents a significant opportunity for upside. We see ADCT-601 in
solid tumors as the early stage program with greatest potential.
ADCT-602
ADCT-602 is the third asset in ADCT's hematology franchise, and the earliest-stage of
the three. The drug is currently engaged in a PhI/II clinical trial for the treatment of
patients with R/R B-cell Acute lymphoblastic leukemia (ALL), as a monotherapy. The IND
for ADCT-602 was accepted by the FDA in July 2018, the first patient was dosed in
November 2018, and management intends to enroll 65 patients, all of whom will have
to have failed prior treatment on a 1st/2nd generation tyrosine kinase inhibitor (TKI).
ADCT-602 utilizes ADCT's proprietary PBD-dimer warhead, affixed using the same linker
technology. The antibody is directed to the CD22 antigen, which has been clinically
validated, and is expressed in >90% of all B-cell acute lymphoblastic leukemia cancers.
Roughly 9,000 patients are diagnosed annually with ALL in the U.S. and EU, roughly
30% of whom will demonstrate relapsed or refractory disease. Despite recent
developments, there remains an opportunity to improve on existing therapies.
Though not explicitly relevant to the preclinical datasets, we note that ADCT-602 was
subject to a clinical hold prior to initiation of the PhI portion of the ongoing clinical trial.
FDA had requested additional detail regarding the stability of the asset at the lower end
of the dose levels.
Interim Data
In January 2020, management released interim data from eight ALL patients treated
with ADCT-602 as part of the ongoing PhI/II trial. Five of eight reported Grade ≥ 3 TEAEs,
30
with the most common being infections and febrile neutropenia, though no dose-limiting
(DLT) has been observed. All patients have discontinued treatment, with one patient
achieving a CR, followed by allogeneic SCT. The dose escalation stage of the trial is
ongoing.
Preclinical Data
Clinical data on ADCT-602, discussed above, has been light. As a result, preliminary
assessments on the drug's efficacy and safety can be made using preclinical data.
The preclinical efficacy of ADCT-602 was evaluated in vivo using the Ramos xenograft
model, whereby mice were administered ADCT-602 (0.3 mg/kg and 1 mg/kg dose levels),
a non-targeted ADC, and a control. Response and tumor volume data were collected,
shown below in Exhibits 28 and 29.
Exhibit 28: Preclinical Efficacy, Ramos Xenograft Model: Response
Data
Exhibit 29: Preclinical Efficacy, Ramos Xenograft Model: Kaplan-Meier
Plot
Source: Company Data
Source: Company Data
Exhibit 30: Preclinical Efficacy, Ramos Xenograft Model: Response Data Table
Exhibit 31:
Source: Company Data
In preclinical safety studies, ADCT-602 was shown to be well tolerated in non-human
primates at the 0.6 mg/kg dose level. Toxicity was observed to be dose-dependent, and
was associated with myelosuppression, loss of body weight, and lymphocyte depletion.
ADCT-601
Next in the early-stage pipeline is ADCT-601, which is part of management's investigatory
efforts in the solid tumor space. The asset targets AXL, which is thought to be
31
overexpressed on a variety of solid tumors, including lung, breast, prostate, pancreatic,
among others. AXL is a receptor tyrosine kinase which is generally associated with poor
clinical prognoses, and is considered to be an attractive target for a variety of reasons:
In addition to being highly expressed on cancer cells, AXL expression is lower in
healthy cells
AXL expression is common in anti-PD1 therapy-resistant tumors, suggesting a
potential for success if used in combination
The AXL antigen can be cleaved to produce 'soluble AXL' (sAXL), which may be used
a biomarker to screen for patients that may respond to treatment with ADCT-601
M2 macrophages, which contribute to the immunosuppressive tumor
microenvironment, express AXL
ADCT-601 has been evaluated in a PhI clinical study as a monotherapy in a variety of
advanced or metastatic solid tumors in patients that have failed other therapies, and the
first patient was dosed in January 2019. Participating patients' cancer types were: triplenegative breast cancer (TNBC), colorectal cancer, esophageal cancer, gastric cancer, and
pancreatic cancer, among others. As of November 4, 2019, 17 patients have been treated,
and the dose escalation stage has been completed (a starting dose of 50 μg/kg up to
150 μg/kg). Two DLTs were observed during dose escalation: one is a Grade 3 hematuria
in a colorectal cancer patient at 100 µg/kg who had a history of radiotherapy involving
the bladder, and the other is a treatment-related hyponatremia in an ovarian cancer
patient at 150 µg/kg. Grade ≥ 3 AEs occurs among 10 patients, with abdominal pain and
urinary tract obstruction being the most common ones. Among 13 patients with
response assessments, one achieved a partial response and seven achieved stable
disease. There has been a request by FDA for management to submit a protocol
amendment before advancing into the PhIb portion of the trial. This amendment is likely
to include the potential evaluation in combination with other therapeutics, or in select
tumor types with high levels of AXL expression.
Preclinical Data
ADCT-601 has been evaluated as part of several different preclinical xenograft models,
including breast cancer (MDA-MB-231), esophageal cancer (ES0195), and pancreatic
cancer (PAXF1657). In the MDA-MB-231 breast cancer xenograft model, ADCT-601
demonstrated sustained tumor suppressive characteristics.
32
Exhibit 32: Preclinical Efficacy, MDA-MB-231 Xenograft Model:
Response Data
Exhibit 33: Preclinical Efficacy, MDA-MB-231 Xenograft Model:
Kaplan-Meier Plot
Source: Company Data
Source: Company Data
Exhibit 34: Preclinical Efficacy, MDA-MB-231 Xenograft Model: Response Data Table
Exhibit 35:
Source: Company Data
Similarly, ADCT-601 has demonstrated efficacy in the ES0195 patient-derived xenograft
esophageal cancer model.
Exhibit 36: Preclinical Efficacy, ES0195 Xenograft Model: Response
Data
Source: Company Data
Exhibit 37: Preclinical Efficacy, ES0195 Xenograft Model: KaplanMeier Plot
Source: Company Data
Exhibit 38: Preclinical Efficacy, ES0195 Xenograft Model: Response Data Table
33
Exhibit 39:
Source: Company Data
ADCT-601 has also been evaluated in the PAXF1657 xenograft pancreatic cancer model,
in parallel with AXL-107-MMAE, which is currently in PhI/II development by Genmab.
The assets are similar, as they both target AXL. A key difference is the warhead, as AXL107-MMAE utilizes monomethyl auristatin E (MMAE) as a cytotoxic warhead, which, as
shown in Exhibit 9 above, is less potent than ADCT's PBD-dimer warhead, SG3199.
As depicted in Exhibit 37 below, at the same dose level (0.3 mg/kg), ADCT-601 had
greater tumor growth suppression, versus AXL-107-MMAE.
Exhibit 40: Response Data, ADCT-6012 vs. AXL-107 MMAE (PAXF1657)
Exhibit 41:
Source: Company Data
Exhibit 42: Preclinical Efficacy, PAXF1657 Xenograft Model: Kaplan-Meier Plot
34
Exhibit 43:
Source: Company Data
Exhibit 44: Preclinical Efficacy, PAXF1657 Xenograft Model: Response Data Table
Exhibit 45:
Source: Company Data
On safety, in non-human primates, safety signals were observed in the subjects' immune
systems, bone marrow, kidneys, females' mammary glands, reproductive systems, and
skin. In rats, the MTD was 6 mg/kg.
ADCT-901
In addition to well-validated targets, management is also developing therapeutics that
target more novel tumor antigens, and ADCT-901 is the first of these efforts. The asset
utilizes ADC's proprietary ADC technology, such as the warhead and linker, but targets
KAAG1, which is commonly expressed in ovarian and triple negative breast cancer, and to
a lesser degree in healthy cells.
Preclinical Data
ADCT-901 is currently being evaluated in the preclinical setting, such as the CTG-0703
ovarian cancer xenograft model. As with many of ADCT's other compounds, the drug has
demonstrated potent tumor growth suppression, shown below.
35
Exhibit 46: ADCT-901 Preclinical Efficacy, CTG-0703 Ovarian Cancer
Model - Response Data Table
Exhibit 47: ADCT-901 Preclinical Efficacy, CTG-0703 Ovarian Cancer
Model - Response Data
Source: Company Data
Source: Company Data
ADCT-701
The last of ADC's publicly disclosed solid tumor assets is ADCT-701, which targets DLK-1,
a transmembrane protein that is typically expressed in healthy fetal tissues, but
expressed in adults on certain types of cancer, such as neuroblastoma, hepatocellular
carcinoma (HCC), and small cell lung cancer (SCLC)(14). Management has expressed
interest in a potential collaboration to continue the development of the asset.
Preclinical Data
The asset has been evaluated in vivo in the LI1097 hepatocellular carcinoma xenograft
model, with results shown below. At the 1 mg/kg dose level, the drug showed the
greatest degree of in vivo tumor growth suppression.
36
Exhibit 48: ADCT-701 Preclinical Efficacy, LI1097 HCC Model - Table
Exhibit 49: ADCT-701 Preclinical Efficacy, CTG-0703 HCC Model Graph
Source: Company Data
Source: Company Data
For all preclinical datasets described above, a PR was reported by evaluators when tumor
volume was ≤ 50% of day 1 volume (for three consecutive measurements), yet ≥ 13.5 mm3
for ≥ 1 of these measurements. A CR was recorded when the tumor volume was <13.5 mm3
for three separate measurements, consecutively. A tumor-free survivor was considered a
subject with an ongoing CR at completion of the study.
Additional Efforts
Beyond the assets described above, management is currently developing five separate
antibody-drug conjugate molecules to further broaden the company's early-stage
pipeline. Among these undisclosed assets are four that are intended for solid tumors,
and one intended for a hematological indication. Further to developing ADCs, several
'XDC' product candidates are in development as well, which intend to utilize structures
other than antibodies to deliver potent cytotoxic warheads to malignant cancer cells.
37
Income Statement
Exhibit 50: ADC Therapeutics Income Statement
Source: Company Data, Morgan Stanley Research estimates
38
Revenues
Exhibit 51: ADC Therapeutics Revenue Summary
Source: Company Data, Morgan Stanley Research estimates
39
Balance Sheet
Exhibit 52: ADC Therapeutics Balance Sheet
Source: Company Data, Morgan Stanley Research estimates
40
Cash Flow Statement
Exhibit 53: ADC Therapeutics Cash Flow Statement
Source: Company Data, Morgan Stanley Research estimates
41
References
1. https://journals.sagepub.com/doi/full/10.1177/0192623318803059?url_ver=Z39.882003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed&
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966843/#s0003title
3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5427099/
4. https://lymphoma.org/aboutlymphoma/nhl/dlbcl/
5. https://lymphoma.org/wpcontent/uploads/2018/05/LRF_FACTSHEET_DIFFUSE_LRG_BCELL_LYMPHOMA_DL
BCL.pdf
6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6142522/
7. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/761121s000lbl.pdf
8. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208194s005lbl.pdf
9. https://www.lls.org/sites/default/files/National/USA/Pdf/Publications/FSHP1_CART_
Factsheet_June2018_FINAL.pdf
10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769601/
11. https://pubmed.ncbi.nlm.nih.gov/26438866/
12. https://acsjournals.onlinelibrary.wiley.com/doi/full/10.3322/caac.21438
13. https://www.mayoclinic.org/diseases-conditions/guillain-barre-syndrome/diagnosistreatment/drc-20363006
14. https://www.mdpi.com/2073-4468/4/2/71/pdf
Other key information sourced from ADC Therapeutics' publicly filed F-1:
https://www.sec.gov/Archives/edgar/data/1771910/000114036120009738/nt10009045x
3_f1.htm
1.
42
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Therapeutics Inc, Genmab A/S, Imara Inc, Moderna Inc, NextCure Inc., Novartis AG, Prevail Therapeutics Inc, Regeneron Pharmaceuticals Inc., Rhythm
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Inc, Fulcrum Therapeutics Inc, Galapagos NV, Genmab A/S, Imara Inc, Insmed Inc, Kaleido Biosciences Inc., Moderna Inc, NextCure Inc., Novartis AG,
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Immunomedics Inc, Incyte Corp, Innoviva Inc, Insmed Inc, Ionis Pharmaceuticals Inc, Ironwood Pharmaceuticals, Inc., Kaleido Biosciences Inc., Kodiak
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Pharmaceuticals Inc, Prevail Therapeutics Inc, Radius Health Inc, Regeneron Pharmaceuticals Inc., Regenxbio Inc, Rhythm Pharmaceuticals Inc, Roche
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Pharmaceutical Holding Company, Biomarin Pharmaceutical Inc, Bluebird Bio Inc, Blueprint Medicines Corporation, Cabaletta Bio Inc, Cytokinetics Inc, DBV
Technologies SA, Denali Therapeutics Inc, Editas Medicine, Epizyme Inc, Evelo Biosciences Inc, Exelixis Inc., Fulcrum Therapeutics Inc, Galapagos NV,
Genmab A/S, Gilead Sciences Inc., Global Blood Therapeutics Inc, Imara Inc, Immunomedics Inc, Incyte Corp, Innoviva Inc, Insmed Inc, Ionis
Pharmaceuticals Inc, Ironwood Pharmaceuticals, Inc., Kaleido Biosciences Inc., Kodiak Sciences Inc, Moderna Inc, MorphoSys AG, MyoKardia Inc, Nabriva
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Regeneron Pharmaceuticals Inc., Regenxbio Inc, Rhythm Pharmaceuticals Inc, Roche Holding AG, Rubius Therapeutics Inc., SAGE Therapeutics Inc,
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43
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(as of May 31, 2020)
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COVERAGE UNIVERSE
STOCK RATING
CATEGORY
Overweight/Buy
Equal-weight/Hold
Not-Rated/Hold
Underweight/Sell
TOTAL
INVESTMENT BANKING CLIENTS (IBC)
OTHER MATERIAL
INVESTMENT SERVICES
CLIENTS (MISC)
COUNT
% OF
TOTAL
COUNT
% OF
TOTAL IBC
% OF
RATING
CATEGORY
COUNT
% OF
TOTAL
OTHER
MISC
1220
1433
5
554
38%
45%
0%
17%
317
336
1
79
43%
46%
0%
11%
26%
23%
20%
14%
550
687
4
227
37%
47%
0%
15%
3,212
733
1468
Data include common stock and ADRs currently assigned ratings. Investment Banking Clients are companies from whom Morgan Stanley received investment
banking compensation in the last 12 months. Due to rounding off of decimals, the percentages provided in the "% of total" column may not add up to exactly
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Other Important Disclosures
44
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INDUSTRY COVERAGE: Biotechnology
COMPANY (TICKER)
RATING (AS OF)
PRICE* (06/08/2020)
E (09/07/2018)
O (03/05/2019)
O (10/11/2019)
O (07/16/2018)
O (04/03/2019)
O (12/05/2019)
U (11/07/2019)
E (03/27/2019)
U (11/21/2019)
E (03/17/2020)
O (09/07/2018)
E (03/02/2020)
E (10/29/2018)
E (04/29/2020)
O (09/12/2018)
$11.82
$130.44
$134.96
$22.70
$74.30
$17.37
$58.83
$10.05
$20.07
$0.79
$20.75
$65.06
$16.99
$44.54
$38.88
O (02/03/2020)
E (10/28/2019)
O (04/09/2020)
E (03/18/2019)
O (09/10/2018)
O (09/10/2018)
O (06/03/2019)
O (07/15/2019)
O (03/27/2019)
O (10/28/2019)
E (09/10/2018)
$94.88
$28.61
$21.11
$22.61
$100.53
$118.51
$30.38
$16.98
$70.67
$50.00
$12.82
David N Lebowitz, CFA, MPH
Akebia Therapeutics Inc (AKBA.O)
Alnylam Pharmaceuticals Inc (ALNY.O)
Ascendis Pharma A/S (ASND.O)
AVROBIO Inc (AVRO.O)
Blueprint Medicines Corporation (BPMC.O)
Epizyme Inc (EPZM.O)
Ionis Pharmaceuticals Inc (IONS.O)
Ironwood Pharmaceuticals, Inc. (IRWD.O)
MacroGenics Inc (MGNX.O)
Nabriva Therapeutics PLC (NBRV.O)
Rhythm Pharmaceuticals Inc (RYTM.O)
Schrodinger Inc. (SDGR.O)
Syndax Pharmaceuticals Inc (SNDX.O)
Y-mABs Therapeutics Inc. (YMAB.O)
Zealand Pharma A/S (ZEAL.O)
Jeffrey Hung
Acceleron Pharma Inc (XLRN.O)
Aprea Therapeutics Inc (APRE.O)
Cytokinetics Inc (CYTK.O)
Exelixis Inc. (EXEL.O)
MyoKardia Inc (MYOK.O)
Neurocrine Biosciences Inc (NBIX.O)
NextCure Inc. (NXTC.O)
Prevail Therapeutics Inc (PRVL.O)
Ultragenyx Pharmaceutical Inc (RARE.O)
Viela Bio (VIE.O)
Voyager Therapeutics Inc (VYGR.O)
Matthew Harrison
46
Alector Inc (ALEC.O)
Alexion Pharmaceuticals (ALXN.O)
Amgen Inc. (AMGN.O)
argenx SE (ARGX.O)
BeiGene Ltd (6160.HK)
BeiGene Ltd (BGNE.O)
Biogen Inc (BIIB.O)
Biohaven Pharmaceutical Holding Company (BHVN.N)
Biomarin Pharmaceutical Inc (BMRN.O)
Bluebird Bio Inc (BLUE.O)
Cabaletta Bio Inc (CABA.O)
Denali Therapeutics Inc (DNLI.O)
Editas Medicine (EDIT.O)
Evelo Biosciences Inc (EVLO.O)
Fulcrum Therapeutics Inc (FULC.O)
Galapagos NV (GLPG.O)
Genmab A/S (GMAB.CO)
Genmab A/S (GMAB.O)
Gilead Sciences Inc. (GILD.O)
Global Blood Therapeutics Inc (GBT.O)
Imara Inc (IMRA.O)
Immunomedics Inc (IMMU.O)
Innoviva Inc (INVA.O)
Insmed Inc (INSM.O)
Kaleido Biosciences Inc. (KLDO.O)
Kodiak Sciences Inc (KOD.O)
Moderna Inc (MRNA.O)
Regeneron Pharmaceuticals Inc. (REGN.O)
Regenxbio Inc (RGNX.O)
Rubius Therapeutics Inc. (RUBY.O)
SAGE Therapeutics Inc (SAGE.O)
Sarepta Therapeutics Inc (SRPT.O)
Seattle Genetics Inc. (SGEN.O)
Unity Biotechnology Inc. (UBX.O)
Vertex Pharmaceuticals (VRTX.O)
Zentalis Pharmaceuticals Inc (ZNTL.O)
O (03/04/2019)
E (12/17/2019)
O (12/17/2019)
O (01/04/2019)
O (01/17/2020)
O (01/17/2020)
U (03/22/2019)
E (04/09/2019)
O (02/07/2017)
E (11/03/2017)
O (11/19/2019)
O (01/02/2018)
E (02/29/2016)
E (05/21/2020)
O (08/12/2019)
E (12/17/2019)
O (08/12/2019)
O (08/12/2019)
E (10/01/2015)
E (03/21/2018)
O (04/06/2020)
E (01/22/2019)
U (08/14/2014)
O (03/21/2018)
E (05/21/2020)
O (10/29/2018)
O (01/02/2019)
E (10/01/2015)
O (11/09/2017)
E (03/13/2020)
O (02/26/2018)
O (08/01/2018)
E (12/10/2019)
O (05/29/2018)
O (10/01/2015)
O (04/28/2020)
$30.88
$119.74
$225.75
$224.30
HK$101.90
$172.88
$301.26
$69.76
$106.87
$69.14
$8.75
$26.08
$27.12
$4.27
$19.99
$201.06
DKr 1,876.00
$28.48
$76.97
$65.84
$51.50
$32.38
$14.24
$28.12
$7.45
$62.50
$59.10
$604.04
$37.34
$6.59
$37.94
$159.68
$150.86
$8.32
$265.01
$47.14
E (10/23/2017)
E (04/29/2020)
E (09/05/2019)
E (05/13/2020)
$5.85
$94.58
$17.90
$13.70
Vikram Purohit
DBV Technologies SA (DBVT.O)
Incyte Corp (INCY.O)
Portola Pharmaceuticals Inc (PTLA.O)
Radius Health Inc (RDUS.O)
Stock Ratings are subject to change. Please see latest research for each company.
* Historical prices are not split adjusted.
© 2020 Morgan Stanley
47
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