ADCs
BioProcess
Insider
eBooks
EVOLVING LINKS IN THE
BIOPHARMACEUTICAL
PIPELINE
Dan Stanton
May 2021
Antibody–Drug Conjugates
Evolving Links in the Biopharmaceutical Pipeline
by Dan Stanton
A Slow Start page 4
From Mylotarg to Zynlonta ADCs page 4
Old Pioneers and Their New Technologies page 8
New Players, New Interests Page 11
Big Pharma on Board page 13
References page 14
About the Author page 16
The number of ADCs that have gained regulatory approval has increased over the
past four years. Advancements in linker technologies and process development are
improving the therapeutic outlooks of these products, catching the attention of
investors. Biomanufacturers now are dedicating substantial research and
development and clinical trial resources into “next-generation” ADC pipelines.
New for 2021, the BioProcess Insider quarterly eBook series reports industry
perspectives about and critical analyses of emerging trends in biopharmaceutical
development, manufacturing, and commercialization. Upcoming topics include the
production capacity and regulatory hurdles to be negotiated by gene-therapy
developers and the COVID-19 pandemic’s long-term effects on vaccine supply chains
and industry investments.
Photo courtesy of Adobe Stock.
Copyright ©2021 INFORMA CONNECT.
All rights reserved.
2
BioProcess International
19(5)E2
MAY 2021
E-Book
YOUR ADC
WITH AJINOMOTO BIO-PHARMA SERVICES,
YOU HAVE THE POWER TO MAKE.
To make your vision a reality. To make your program a success.
To make a positive difference in the world.
Our ADC service offerings simplify your complex supply chain by
consolidating process development/transfer, analytical development, GMP
bioconjugation, purification and fill finish services all at a single location.
ADC SERVICES:
Conjugation & Purification
Fill Finish & Lyophilization
Process Development
Analytical Development
Packaging & Labeling
AJICAP™ Technology
WHAT DO YOU
WANT TO MAKE?
www.AjiBio-Pharma.com
T
he number of antibody–drug conjugate (ADC) products that
have gained regulatory approval has reached double-digit
figures, and ADC developers both old and new are talking
about the next generation of drug candidates coming
through their pipelines. In April 2021, Zynlonta (loncastuximab
tesirine from ADC Therapeutics) became the eleventh ADC product
to receive approval from the US Food and Drug Administration
(FDA) (Table 1) (1). But with dozens of ADC candidates currently in
clinical trials, those 11 products represent the tip of the ADC iceberg
(2). To understand how this modality is likely to evolve and to try to
define the different generations of ADCs, it is worth investigating
their history and regulatory approval patterns.
A Slow Start
Eleven years passed between the approval of Mylotarg
(gemtuzumab ozogamicin, developed by Wyeth and Celltech) and
the next ADC approval. When Adcetris (brentuximab vedotin from
Seagen, formerly Seattle Genetics) received approval in 2011, it was
the sole ADC on the market because Pfizer — which bought Wyeth’s
pharmaceutical business in 2009 — had pulled its Mylotarg
product from the market the previous year (3). Over the subsequent
five years, only one other ADC, Kadcyla (ado-trastuzumab
emtansine from Roche) garnered thumbs up from the FDA. But in
2017, the number of ADCs on the market doubled as Pfizer
commercialized Besponsa (inotuzumab ozogamicin) and gained
Mylotarg reapproval (4). In 2018, one more ADC reached the
market. But since 2019, the number of approvals brought about a
relative tidal wave: six more ADCs, including the aforementioned
Zynlonta product.
However, different generations of ADCs cannot be defined only
by the dates of their approvals. ADCs comprise a potent small
molecule warhead, a targeting antibody, and a linker that attaches
them both. Ongoing research and development in each of those
three individual elements along with their combinations mean
that a “next-generation” label can be nothing more than a
successful scientific tweak that further tips the efficacy–toxicity
balance toward the former. ADCs are complex, multicomponent
molecules, incorporating the drug development difficulties of both
an antibody and a highly toxic small molecule, so evolution of the
modality is not a linear path, says Shawn Novick, principal
consultant at Biophia Consulting and former director of the
quality control department at Seagen. “Clearly the drug and the
linker make a big difference, and people are still trying to figure
those out.”
Back to Contents
From Mylotarg to Zynlonta ADCs
The history of the Mylotarg product is the best case study to
evaluate. That ADC was ill-fated because of the instability of its
cleavable linker, which included a hydrazone bond that releases
the cytotoxic agent calicheamycin prematurely in plasma
4
BioProcess International
19(5)e2
May 2021
E-Book
Energizing pharma
New empowering
GEA Pharma portfolio
GEA Pharma Separators aseptic and pure –
for highest hygienic demands and utmost
variability for your process
Join us at for a new era of processing! GEA experts have transformed
decades of separation experience into a new, complete selection of
plug & produce skids – infinitely adaptable to take all pharma customers
to the next level!
gea.com/energizing-pharma
Table 1: Approved antibody–drug conjugates (ADCs)
Drug
Gemtuzumab
ozogamicin
Brentuximab
vedotin
Trastuzumab
emtansine
Inotuzumab
ozogamicin
Moxetumomab
pasudotox
Polatuzumab
vedotin
Enfortumab
vedotin
Trastuzumab
deruxtecan
Sacituzumab
govitecan
Maker
Pfizer/Wyeth
Condition
Trade Name
Seattle Genetics,
Hodgkin’s lymphoma (HL) and systemic, anaplastic, large-cell lymphoma
Millennium/Takeda (ALCL)
Genentech, Roche HER2-positive metastatic breast cancer (mBC) following treatment with
trastuzumab and a maytansinoid
Pfizer
Relapsed or refractory CD22-positive B-cell precursor acute
lymphoblastic leukemia
AstraZeneca
Relapsed or refractory hairy-cell leukemia (HCL)
Adcetris
2017 (originally
2000)
2011
Kadcyla
2013
Besponsa
2017
Lumoxiti
2018
Genentech, Roche
Relapsed or refractory diffuse large B-cell lymphoma (DLBCL)
Polivy
2019
Astellas/Seattle
Genetics
AstraZeneca/
Daiichi Sankyo
Immunomedics
Adult patients with locally advanced or metastatic urothelial cancer who
have received a PD-1 or PD-L1 inhibitor and a Pt-containing therapy
Adult patients with unresectable or metastatic HER2-positive breast
cancer who have received two or more anti-HER2–based regimens
Adult patients with metastatic triple-negative breast cancer (mTNBC) who
have received at least two previous therapies and for patients with
relapsed or refractory metastatic disease
Multiple myeloma patients whose disease has progressed despite
treatment with an immunomodulatory agent, proteasome inhibitor, and
anti-CD38 antibody
Relapsed or refractory large B-cell lymphoma (including DLBCL arising
from low-grade lymphoma, DLBCL of unspecified origin/etiology, and
high-grade B-cell lymphoma) after two or more lines of systemic therapy
Padcev
2019
Enhertu
2019
Trodelvy
2020
Blenrep
2020
Zynlonta
2021
Belantamab
mafodotin
GlaxoSmithKline
Loncastuximab
tesirine
ADC Therapeutics
Relapsed acute myelogenous leukemia (AML)
Mylotarg
Approval
Year
circulation. That led to the 2010 withdrawal. By tweaking the dose
level of the payload, modifying the administration schedule, and
targeting a different patient population, however, Pfizer and Wyeth
gained FDA reapproval in 2017.
That same linker technology is used in Pfizer’s Besponsa ADC.
Arguably, the Mylotarg product’s reversal of fortune came from
Pfizer’s continued R&D efforts in the ADC space in the five years
after pulling its Mylotarg product. Thus, the linker technology does
not define the 17-year gap between the Mylotarg and Besponsa
products, but rather, it represents the scientific evolution of how a
linker interacts with a payload and monoclonal antibody (MAb).
Note that Pfizer licensed out its ADC technology to Pyxis
Oncology, along with its two preclinical assets known as PYX-201
and PYX-203 (5). The platform includes different payload classes,
site-specific conjugation techniques, and an evolved version of the
linker technology in both Mylotarg and Besponsa products. The
“second-generation” ADCs have different linkers: a noncleavable
linker in the Kadcyla product and Seagen’s cathepsin-cleavable
technology in Adcetris, Padcev (enfortumab vedotin from Astellas/
Seattle Genetics), and Polivy (polatuzumab vedotin from
Genentech/Roche) ADCs (6). Both technologies offer advantages in
terms of stability and toxicity over “first-generation” linker
technologies but still are subject to their own limitations.
But ADCs are not defined by their linkers alone. “The toxicity of
a drug and its ability to infiltrate the cell” also are critical to
6
BioProcess International
19(5)e2
May 2021
Back to Contents
E-Book
HEARD THE BUZZ ?
ZZ
WE’RE PUTTING THE STING IN YOUR TARGETED THERABEES!
A RELIABLE CDMO PARTNER FOR
ADC PROCESS DEVELOPMENT & MANUFACTURING
› Purpose-built Bioconjugation facility
› ADC conjugation expertise
› Experienced supplier of ADC payloads
› Fast-track offer for first samples
› cGMP clinical & commercial manufacturing
› Integrated supply chain
› Leader in preparative chromatography
› Excellent regulatory history
LEARN MORE
understand, says Novick. She adds that the development of the
Adcetris product included much time spent on determining how
toxic its antimitotic agent, monomethyl auristatin E (“vedotin”),
needed to be. With Immunomedic’s Trodelvy (sacituzumab
govitecan) approved nine years after the Adcetris ADC, the low
toxicity of its cytotoxic payload SN-38 showed a high efficacy level,
which “was surprising to the community” but demonstrated the
critical balance among the warhead, the MAb, and the linker (in
this case, a new hydrolyzable linker).
Conversely, whereas the Troveldy ADC’s success centered on the
low toxicity of its small molecule, ADC Therapeutics’s Zynlonta
(loncastuximab tesirine) product stood out for the high toxicity of
its pyrrolobenzodiazepine (PBD) dimer payload. PBDs are a class of
compounds that kill cells by binding their DNA and interfering
with replication. In nature, they are made by a group of bacteria
known as actinomycetes but were developed by Spirogen, (from
which ADC Therapeutics spun out in 2013) for use in medicine.
PBDs are a useful alternative to cytotoxic payloads such as
calicheamycin because they are not cross-resistant with other
chemotherapy agents (7). They also have a unique mode of action
that sets them apart from the tubulin binders such as
maytansinoids and auristatins, which currently dominate the ADC
arena.
The different ADCs that have reached the market show that no
single element is driving the evolution of the modality. As
Penelope Drake, head of R&D for bioconjugates at Catalent tells us:
“Each element — target selection, antibody discovery, optimization,
conjugation site, linker chemistry, and payload selection — factors
heavily into the success or failure of a program.” The combination
of those parts is key.
Old Pioneers and Their New Technologies
Clay Siegall, ADC innovator and chief executive officer of Seagen,
offered up his take on the difference in the generations of ADC
products already on the market and those that are coming through
the pipeline (Figure 1). “The field is now really taking on a life of
its own, and a lot of companies now work on ADCs,” he told
shareholders in April 2021 (8). “I look at the past ADCs and how
they were made with bad linkers and natural-product drugs, and I
call that ‘ADCs 1.0.’ Then there were better drugs, synthetic drugs,
and much better linkers that are in drugs such as Adcetris, Padcev,
and Polivy from Roche, and others. And I call those ‘ADCs 2.0.’”
Since the arrival of the Adcetris ADC, Siegall has expanded his
company’s proprietary and partnered pipeline (9). His team is
investigating a PBD dimer as a highly potent cytotoxic agent, while
collaborating with biomanufacturers such as Roche (such as in the
case of the Polivy ADC), GlaxoSmithKline, Genmab, and Pfizer.
Seagen also has licensed its linker technology to companies,
including AbbVie, Astellas, Bayer, Celldex, Genentech,
GlaxoSmithKline, Pfizer, and Progenics.
8
BioProcess International
19(5)e2
May 2021
Back to Contents
E-Book
YOUR
GLOBAL
DUAL
SOURCE
FOR
BIOLOGICS
Capabilities Include:
GMP Production Where
and When You Need It.
Quality. Expertise. Performance. Capacity. These are the four
Drug Substance (DS) Manufacture
• 150,000 L bioreactor capacity,
expanding to 430,000 L after 2024
• Single-use/disposable bioreactors
• Scale-out manufacturing paradigm
• Fed-batch or continuous cell culture
cornerstones WuXi Biologics provides to its clients with every biologic
Drug Product (DP) Manufacture
produced. We are operating 10 state-of-the-art world-class cGMP DS
• Ten automated, isolator-based
fill lines
facilities and another 10 DP facilities across four countries while
expanding globally over the next few years. WuXi Biologics provides
high-quality DS and DP where and when you need it. Let’s Get Started.
China • Germany • Ireland • Singapore • United States
www.wuxibiologics.com
• Vial or pre-filled syringe and liquid
or lyophilization fill options
• Ready-to-Use (RTU) containers and
closures available
Figure 1: Seagen’s clinical development pipeline (https://www.seagen.com/assets/pdfs/Our-Science/Pipeline/SeagenPipeline.pdf)
Siegall continued, rhetorically asking how the ADC industry can
move to a third generation of products and implement technologies
that continue to improve efficacy in patients and decrease side
effects. “We’ve spent many years pioneering new technologies, and
I am really jazzed up about those new technologies based on all of
their preclinical data in efficacy and in safety, including [from]
nonhuman primates.”
For now, however, details from Seagen remain behind closed
laboratory doors. “What you’ll see from us is another generation of
new ADCs that may have different payloads, different linkers, [and]
different ways of thinking about how to do these different
toxicities or lack thereof. Those are coming. We are working hard
on ‘ADCs 3.0.’ So stay tuned.”
Big biopharmaceutical developer AbbVie has had a more
turbulent relationship with ADCs. In 2016, the company spent
US$5.8 billion to acquire Stemcentrx (10), citing its candidate lung
cancer ADC Rova-T (rovalpituzumab tesirine) as a major driver. In
August 2019, however, Abbvie halted development after the drug
demonstrated no survival benefit in clinical trials (11). The
10
BioProcess International
19(5)e2
May 2021
Back to Contents
E-Book
company still has a program in phase 2 clinical trials with
telisotuzumab vedotin (ABBV-399), an ADC targeting c-Met to treat
non–small-cell lung cancer.
“Approaches in this area historically have focused on smallmolecule kinase inhibitors and anti–c-Met antibodies, both of
which have shown only limited efficacy in this patient population,
which has not been sufficient for approval,” AbbVie president Mike
Severino said during a Q1 2021 conference call (12). “By contrast,
our c-Met antibody–drug conjugate is a novel approach that we
believe will have broader applicability and will provide enhanced
efficacy compared with previous approaches.”
But Severino also spoke candidly about a “next-generation” c-Met
ADC program set to enter clinical trials later this year. “Our new
c-Met ADC, ABBV-400, uses a topoisomerase inhibitor payload,
which we believe will provide greater antitumor efficacy against
both amplified Met and over-expressed c-Met subtypes, thus
providing deeper responses with broader applicability than other
anti–c-Met targeting agents.”
Similarly, AstraZeneca saw success with partner Daiichi Sankyo
with anti–human epidermal growth factor receptor 2 (anti-HER2)
ADC Enhertu (fam-trastuzuab deruxtecan). Now the company wants
to bolster its position in the breast cancer field further through
datopotamab deruxtecan (DS-1062), consisting of a humanized antiTROP2 MAb and a topoisomerase I inhibitor payloa, which is
currently in phase 3 clinical trials. “The payload TROP1 versus SN38
is 10 times more potent. We have a highly stable linker. The half-life
of DS-1062 is five days, so we can have a convenient three-week
schedule,” Cristian Massacesi, senior vice president of AstraZeneca’s
late-stage oncology R&D unit said, last month (13).
New Players, New Interests
In 2019, about 80 ADCs were in clinical development through
nearly 600 clinical trials (14). Although current figures are
difficult to determine — some market reports claim that nearly 250
unique ADC product candidates are under development (15) — the
numbers are increasing, spurred by recent commercial successes.
According to a 2020 report from Beacon Intelligence, the past 10
years have brought a linear growth in the number of ADC trials
initiated per year, with a compound annual growth rate (CAGR) of
new trials of 15.7% (16).
“After many years of expectations, it is only recently, thanks to
multiple new drug launches, that ADC therapies finally have
fulfilled their promise,” explains Kevin Daley, market director of
pharmaceuticals at Novasep. “The clinical pipeline continues to
strengthen, and the pharmaceutical innovator ‘pioneers’ of ADCs
now have been joined by many new entrants, both large pharma
and small biotech companies, with technical advances, (such as
site-specific conjugation) leading to more effective ADCs.”
Catalent’s Drake adds that “much of the new pipeline growth has
been driven by small and virtual biotech companies, but mid-sized
11
BioProcess International
19(5)e2
May 2021
Back to Contents
E-Book
Table 2: Investments and money raised by antibody–drug conjugate (ADC) companies in 2020 and 2021
Money Raised
(Millions)
Select ADC Information
Company Name
Funding Type
Velos Bio
Series B
Dyne Therapeutics
Araris Biotech
IPO
Seed
$268
CHF 12.7
Remegen
IPO
$515
Silverback Therapeutics IPO
$241
Bolt Biotherapeutics
IPO
$230
New class of oligonucleotide-based therapies
Matched protein–drug conjugates by combining proprietary
novel technologies with disease-specific biology
ROR1-directed ADC (the company has since been bought by
Merck)
Antibody–antisense conjugate
Linker for attachment of any payload to “off-the-shelf”
antibodies without antibody engineering
“Uniquely positioned in China with an in-house, fully
integrated end-to-end ADC platform”
ADCs based on ImmunoTAC platform, which attaches
antibodies to small molecules that adjust the immune system
Immune-stimulating antibody conjugates (ISACs)
Suzhou Medilink
Therapeutics
Pyxis Oncology
Series A
$50
“More efficacious and safer ADC drug”
March 2021
Series B
$152
Licensed technology and assets from Pfizer
March 2021
Cybrexa Therapeutics
Series B
$21
Alphalex peptide–drug conjugate (PDC)
March 2021
Adcendo
–
€51
April 2021
Adcentrx Therapeutics
Series A
$50
ADCs using uPARAP, a cell-surface receptor involved in
collagen degradation cloned and characterized by the
scientific founders
No details available
Mablink Bioscience
Seed
€4
Uses proprietary PSARlink technology to link cytotoxic
molecules to antibodies
April 2021
Avidity Biosciences
Tubulis
IPO
Series A
$298
€10.7
$137
and large pharma [companies] also have been very active in the
space by developing their own ADCs or by looking for opportunities
to in-license or acquire ADC programs.”
Daley and Drake point to the diverse mix of companies taking
up the ADC baton. For example, Byondis (previously Synthon
Biopharmaceuticals) and Mersana Therapeutics, are mid-sized
clinical stage biotechnology companies yet to commercialize a
product, but each one hopes to be the next Seagen if and when
assets blossom. Byondis’s trastuzumab duocarmazine (SYD985) is
the latest in a wave of ADCs directed by HER2. Mersana’s lead
asset upifitamab rilsodotin (UpRi) is in phase 2 clinical studies
as a treatment for ovarian cancer and is based on the company’s
Dolaflexin platform. That technology uses the proprietary
Fleximer polymer, a biodegradable, biocompatible, water-soluble
polymer that can carry multiple drug molecules attached through
a cleavable linker to a scaffold, which is then conjugated to the
antibody through a noncleavable linker.
BioAtla, which formed around the same time as those two
companies, also falls in this category of new ADC companies. It
uses antibodies that can be activated or inactivated under defined
physiological conditions in its ADC development, with the
conditionally active biologic (CAB)–ADCs platform allowing the
preferential targeting of tumor tissues while reducing the toxicity
of the warhead.
But numerous start-ups also want to take their place in the ADC
industry, and it appears that the money is available to support
12
BioProcess International
19(5)e2
May 2021
Date
July 2020
July 202
July 2020
September 2020
October 2020
November 2020
December 2020
February 2021
April 2021
Back to Contents
E-Book
them throughout their growth. Even with the global pandemic in
full thrust, ADC Therapeutics raised $267 million in May 2020 (17)
through an initial public offering (IPO). But much of the other
investments in the past year have focused on early stage, drug
conjugate, small- and medium-sized entities (SMEs), including
those listed in Table 2.
Big Pharma on Board
A good sign that a sector is robust is when investments are high
and private equities and venture capitals are fluid. Further proof
that the ADC sector is becoming a major part of the
biopharmaceutical landscape is the entry and renewed interest of
Big Pharma. Major players such as Pfizer, AstraZeneca, Roche, and
GSK have been — and continue to be — heavily invested in ADCs.
And the excitement in the field has brought others on board.
In September 2020, Gilead Sciences announced a $21 billion deal
to buy Immunomedics (18). Although revenues from the recently
approved Trodelvy ADC were a key driver in the deal, management
said the acquisition was an opportunity to secure an ADC platform
for future products. “A lot of people have been struggling with
ADCs for a long time,” said chief medical officer Merdad Parsey.
“We’re excited about what we’re seeing on the therapeutic potential
here of this platform. The ability to deliver a payload here with this
particular linker is promising in triple-negative [breast cancer], so
we have to think about what other antibodies and other antigens
we could go after to try to expand the utility.”
Merck & Co. (known as MSD outside of North America) became
another entrant in the ADC space in 2020. First, the company
entered into a strategic development collaboration with Seagen in
September (19). The deal, which included Merck buying a $1 billion
stake in its new partner, involves codevelopment of ladiratuzumab
vedotin, an investigational ADC targeting LIV-1 in phase 2 clinical
trials for breast cancer and other solid tumors. Weeks later, Merck
went all in and bought phase 2 ADC developer VelosBio for $2.75
billion (20).
Boehringer Ingelheim’s €1.18 billion ($1.4 billion) acquisition of
private Swiss biotech NBE Therapeutics in December (21) brought
the Germany-headquartered pharmaceutical developer an ADC
technology platform and a lead compound: NBE-002 in phase 1
clinical studies for triple-negative breast cancer and other solid
tumors. And that was not the company’s first ADC deal.
“Boehringer Ingelheim was active previously in the field with a
first-generation ADC technology,” spokesman Reinhard Malin told
BPI Insider when the deal was announced. “With the acquisition of
NBE Therapeutics, we have reentered the space with an innovative,
next-generation technology, which expands our activities in tumorcell–targeting approaches.” In the early 2000s, Boehringer
Ingelheim filed several patents (22, 23, for example) for antibodyconjugate technologies. However, no commercialized ADCs resulted
from those.
13
BioProcess International
19(5)e2
May 2021
Back to Contents
E-Book
Commercial pharmaceutical company Exelixis also is viewing
ADCs as the natural extension to its heritage of developing novel
small-molecules, and it has signed a number of deals in the past
12 months. In September 2020, Exelixis paid NBE Therapeutics
$25 million to develop ADCs using NBE Therapeutics’s
conjugation and novel anthracycline-based payload platform (24),
while simultaneously teaming with Catalent for access to
SMARTag site-specific bioconjugation technology. And in March,
Exelixis made what it describes as a “modest” payment to
Chinese drugmaker WuXi Biologics for exclusive license to a
panel of MAbs to a preclinically validated target, intended for the
development of ADCs.
“We really like the ADC space . . . It’s the ultimate Venn diagram
view of chemistry and biology kind of merging together,” chief
executive officer Michael Morrissey told investors at the 2021
Barclays Global Healthcare Conference earlier this year (25), before
adding that his company intends to go full throttle on the
modality. “We’re not going to just dabble and do a little bit here or
there and see what happens. If we’re convinced and we have
conviction in a technology and our ability to navigate and bring in
new science, then we’re going to go in strong with the right level of
resources and the right level of both financial and human capital
to be able to move the needle there.”
Further evidence of the strength of the ADC market is evident in
the 2020 sales for select commercialized therapies, including
• Adcetris product: $658 million for Seagen, JPY 59.4 billion
($542 million) for Takeda (FY ending 31 March 2021)
• Kadcyla product: CHF 1.75 billion ($1.92 billion) for Roche,
JPY 10.2 billion ($93 million) for subsidiary Chugai
• Padcev product: $222 million for Seagen, JPY 12.8 billion
($117 million) for Astellas (FY ending 31 March 2021)
• Polivy product: CHF 169 million ($186 million) for Roche.
Thus, with money flowing, deals in the making, and agencies
regulating, ADCs finally have established themselves as part of the
healthcare landscape that is likely to have a bright and lucrative
future.
References
1 Stanton D. ADC Therapeutics Joins Conjugate Elite with Zynlonta FDA
Back to Contents
Approval. BioProcess Insider 27 April 2021; https://bioprocessintl.com/
bioprocess-insider/regulations/adc-therapeutics-joins-conjugate-elite-withzynlonta-fda-approval.
2 Global Antibody–Drug Conjugate (ADC) Clinical Trial Review. Creative
Biolabs: Shirley, NY; https://www.creative-biolabs.com/resource/adc/pdf/com/
downloads/Global-Antibody-drug-Conjugate-ADC-Clinical-Trial-Review.pdf.
3 Hall J, Krauskopf L. Pfizer to Buy Wyeth for $68 Billion. Reuters, 25
January 2009; https://www.reuters.com/article/us-wyeth-pfizer/pfizer-to-buywyeth-for-68-billion-idUSTRE50M1AQ20090126.
14
BioProcess International
19(5)e2
May 2021
E-Book
4 FDA Approves Mylotarg for Treatment of Acute Myeloid Leukemia. US Food
and Drug Administration, 1 Septemer 2017; https://www.fda.gov/news-events/
press-announcements/fda-approves-mylotarg-treatment-acute-myeloidleukemia.
5 Pyxis Oncology Presents Preclinical Data and Details on Antibody–Drug
Conjugate Candidates Supporting Therapeutic Potential. Pyxis Oncology, 27 April
2021; https://www.globenewswire.com/fr/news-release/2021/04/27/2217631/0/
en/Pyxis-Oncology-Presents-Preclinical-Data-and-Details-on-Antibody-DrugConjugate-Candidates-Supporting-Therapeutic-Potential.html.
6 Joubert N, et al. Antibody–Drug Conjugates: The Last Decade.
Pharmaceuticals (Basel) 13(9) 2020: 245; https://www.ncbi.nlm.nih.gov/pmc/
articles/PMC7558467/#B10-pharmaceuticals-13-00245.
Back to Contents
7 Pyrrolobenzodiazepine (PBD). ADC Review; https://www.adcreview.com/
pyrrolobenzodiazepine-pbd.
8 Seattle Genetics (SGEN) Q1 2021 Earnings Call Transcript. Motley Fool 29
April 2021; https://www.fool.com/earnings/call-transcripts/2021/04/30/seattlegenetics-sgen-q1-2021-earnings-call-transc.
9 Stanton D. Beyond Adcetris: Seattle Genetics Aiming for Big Biopharma
Status. BioProcess Insider 30 April 2018; https://bioprocessintl.com/bioprocessinsider/therapeutic-class/beyond-adcetris-seattle-genetics-aiming-for-bigbiopharma-status.
10 AbbVie to Expand Oncology Presence Through Acquisition of Stemcentrx
and Its Novel Late-Stage Rova-T Compound for Small Cell Lung Cancer. AbbVie 28
April 2016; https://news.abbvie.com/news/abbvie-to-expand-oncology-presencethrough-acquisition-stemcentrx-and-its-novel-late-stage-rova-t-compound-forsmall-cell-lung-cancer.htm.
11 AbbVie Discontinues Rovalpituzumab Tesirine (Rova-T) Research and
Development Program. Cision PR Newswire 29 August 2019; https://www.
prnewswire.com/news-releases/abbvie-discontinues-rovalpituzumab-tesirinerova-t-research-and-development-program-300909121.html.
12 AbbVie (ABBV) Q1 2021 Earnings Call Transcript. The Motley Fool 30 April
2021; https://www.fool.com/earnings/call-transcripts/2021/04/30/abbvie-abbvq1-2021-earnings-call-transcript.
13 AstraZeneca PLC’s (AZN) CEO Pascal Soriot on Q1 2021 Results: Earnings
Call Transcript. Seeking Alpha, 30 April 2021; https://seekingalpha.com/
article/4423281-astrazeneca-plcs-azn-ceo-pascal-soriot-on-q1-2021-resultsearnings-call-transcript.
14 Coats S, et al. Antibody–Drug Conjugates: Future Directions in Clinical
and Translational Strategies to Improve the Therapeutic Index. Clin. Cancer Res.
25(18) 2019: 5441; https://doi.org/10.1158/1078-0432.CCR-19-0272.
15 ADC Contract Manufacturing Market, 4th Edition. Roots Analysis, January
2021; https://www.rootsanalysis.com/reports/view_document/adc-contractmanufacturing-market/218.html.
16 Beacon ADC Landscape Inforgraphic H1 2020; Beacon Targeted Therapies;
https://beacon-intelligence.com/adc-h1-2020-landscape-infographic.
17 ADC Therapeutics Announces Closing of Upsized $267 Million Initial
Public Offering and Receipt of the $65 Million First Tranche Under Its $115
Million Convertible Credit Facility with Deerfield. Business Wire 19 May 2020;
https://www.businesswire.com/news/home/20200519005941/en/ADCTherapeutics-Announces-Closing-of-Upsized-267-Million-Initial-Public-Offeringand-Receipt-of-the-65-Million-First-Tranche-under-Its-115-Million-ConvertibleCredit-Facility-with-Deerfield.
15
BioProcess International
19(5)e2
May 2021
E-Book
18 Vinluan F. Gilead Adds ‘Cornerstone’ Cancer Drug in $21bn
Immunomedics Buyout. BioProcess Insider, 14 September 2020; https://
bioprocessintl.com/bioprocess-insider/deal-making/gilead-adds-cornerstonecancer-drug-in-21bn-immunomedics-buyout.
19 Seattle Genetics and Merck Announce Two Strategic Oncology
Collaborations. Merck press release, 14 September 2020; https://www.merck.
com/news/seattle-genetics-and-merck-announce-two-strategic-oncologycollaborations.
20 Merck to Acquire VelosBio. Merck press release, 5 November 2020; https://
www.merck.com/news/merck-to-acquire-velosbio.
21 Stanton D. Boehringer Ingelheim Re-enters ADC Space with $1.4bn NBE
Buy. BioProcess Insider, 11 December 2020; https://bioprocessintl.com/
bioprocess-insider/deal-making/boehringer-ingelheim-re-enters-adc-space-with1-4bn-nbe-buy.
22 Günther A, Baum A, Heider K-H. EP1391213A1: Compositions and Methods
for Treating Cancer Using Maytansinoid CD44 Antibody Immunoconjugates and
Chemotherapeutic Agents. European Patent Office; https://patents.google.com/
patent/EP1391213A1/en.
23 Garidel P, et al. DE10361599A1: Liquid Formulation of Antibody Conjugates.
European Patent Office; https://patents.google.com/patent/DE10361599A1/en.
24 Stanton D. Exelixis: Deals with NBE and Catalent Bring Multipronged ADC
Approach. BioProcess Insider, 17 September 2020; https://bioprocessintl.com/
bioprocess-insider/deal-making/exelixis-deals-with-nbe-and-catalent-bringmulti-pronged-adc-approach.
25 Exelixis, Inc. (EXEL) CEO Michael Morrissey on Barclays Global Healthcare
Conference (Transcript). Seeking Alpha, 13 March 2019; https://seekingalpha.
com/article/4248478-exelixis-inc-exel-ceo-michael-morrissey-on-barclaysglobal-healthcare-conference-transcript.
About the Author
Dan Stanton is founding editor of BioProcess Insider; dan.
stanton@informa.com.
16
BioProcess International
19(5)e2
May 2021
Back to Contents
E-Book