Item 7. Management's Discussion and Analysis of
Financial Condition and Results of Operations.
You should read the following
discussion and analysis of our financial condition and results of
operations together with our financial statements and related notes
appearing at the end of this Annual Report on Form 10-K. Some of
the information contained in this discussion and analysis or set
forth elsewhere in this Annual Report on Form 10-K, including
information with respect to our plans and strategy for our business
and related financing activities, includes forward-looking
statements that involve risks and uncertainties. You should read
the "Risk Factors" section of this Annual Report on Form 10-K, Item
1A, for a discussion of important factors that could cause actual
results to differ materially from the results described in or
implied by the forward-looking statements contained in the
following discussion and analysis.
Overview
We are a clinical stage
biopharmaceutical company primarily focused on developing
proprietary therapeutics designed to extend life or improve quality
of life for cancer patients. We are building a drug development
pipeline through the licensing and acquisition of therapeutics in
late preclinical and clinical development stages. We leverage our
scientific and clinical experience to help reduce the risk of and
accelerate the clinical development of our drug product
candidates.
In December 2019, we
completed our initial public offering (including the exercise of
the over-allotment by the underwriters) by selling 1,277,778 shares
of our common stock at a public offering price of $8.00 per share.
Net proceeds were approximately $9.4 million, after deducting
underwriting discounts and accrued, unpaid offering expenses. Our
common stock began trading on the Nasdaq Capital Market on December
19, 2019.
In January 2020, we entered
into a Capital on DemandTM Sales Agreement
with JonesTrading Institutional Services, LLC
(“JonesTrading”), as sales agent, pursuant to which we
offered and sold (at our discretion), from time to time, through or
to JonesTrading shares of our common stock, having an aggregate
offering price of up to $19.7 million. Pursuant to this agreement,
through December 31, 2020, we have sold 860,677 shares of our
common stock at an average gross price of $9.79 per share for net
proceeds of $8,175,290, after fees and commissions of $253,036.
From January 1, 2021 through February 11, 2021, we sold an
additional 1,104,047 shares of our common stock at an average gross
price of $10.20 per share for net proceeds of $10,925,311, after
fees and commissions of $338,153.
In June 2020, we entered into
a 50/50 collaboration development agreement with NorthStar Medical
Radioisotopes, LLC (“NorthStar”) to develop potential
Radio-Immuno-Therapeutics (“RITs”) to treat severe
COVID-19 (patients with SARS-CoV-2 infection). NorthStar is a
commercial producer and supplier of medical radioisotopes. This
collaboration combines NorthStar’s expertise in the
innovative production, supply, and distribution of important
medical radioisotopes with our expertise in therapeutic drug
development and our pre-IND stage humanized urokinase plasminogen
activator receptor (“uPAR”) targeted monoclonal
antibody known as MNPR-101, along with a proprietary portfolio of
related monoclonal antibodies that target uPAR or its ligand uPA.
uPAR seems to be selectively expressed on aberrantly activated
immune cells. In response to coronavirus infection, these rogue
immune cells produce pro-inflammatory cytokines that can cause
runaway inflammation throughout the body, commonly referred to as a
cytokine storm. It is this systemic hyper-inflammatory state that
is thought to be largely responsible for the severe lung injury and
multiple organ damage that contributes to poor outcomes and death
in patients with severe COVID-19.
In this collaboration, we
have coupled MNPR-101 to therapeutic radioisotopes supplied by
NorthStar. The resulting conjugates are designed to be a highly
selective agents that have the potential to kill aberrantly
activated cytokine-producing immune cells. By eradicating these
cells with a uPAR-targeted RIT (“uPRIT”), the goal is
to spare healthy cells while quickly reducing the cytokine storm
and its harmful systemic effects. Through March 5, 2021, we have
incurred immaterial amounts of expenses related to the NorthStar
collaboration, while partnering with several key companies and
institutions to further the collaboration’s development
efforts. These collaborators include: IsoTherapeutics Group, LLC,
which generated the uPRIT candidates; Aragen Bioscience Inc., which
screened the uPRIT candidates through preclinical biochemical
testing; and Texas Lung Injury Institute / University of Texas
Health Science Center at Tyler, which plans to perform preclinical
testing and, if successful, clinical testing.
In August 2020, we announced
a plan to develop a test to potentially triage COVID-19 patients
into those likely versus unlikely to progress to severe respiratory
failure. The test would use our proprietary monoclonal antibody,
ATN-658, to detect soluble urokinase plasminogen activator receptor
(“suPAR”) in COVID-19 patient plasma. A suPAR test for
COVID-19 patients, if successful, could identify those at high risk
for severe respiratory failure, facilitating earlier therapeutic
interventions and/or allowing for the staging of patients to an
optimal treatment based on their disease
characteristics.
57
In November 2020, we
announced a series of recently issued patents for our Phase 2b/3
clinical-stage lead product candidate, Validive (clonidine HCl
mucobuccal tablet). These patents, including U.S. Patent No.
10,675,271, provide claims covering “Clonidine and/or
clonidine derivatives for use in the prevention and/or treatment of
adverse side effects of chemotherapy”. These patents expand
the potential use of Validive in cancer patients, beyond the
earlier allowed claims for the prevention of oral mucositis in
patients receiving CRT. Specifically, they provide protection for
the potential ability of Validive to prevent or treat common
chemotherapy-associated side effects such as asthenia and fatigue
and would provide protection should we determine in the future to
conduct additional Validive development activities related to
adverse side effects of chemotherapy beyond oropharyngeal
cancer.
In December 2020, we
announced the issuance of a U.S. patent (US 10,450,340) covering
compositions of matter (2-pyrrilino camsirubicin) for a novel
family of camsirubicin analogs. This patent, which expands the
Company’s camsirubicin intellectual property portfolio, is
expected to expire in 2038 not including any patent term
extensions. The patent broadens our camsirubicin portfolio and
creates a pipeline that has been designed to retain the potentially
favorable non-cardiotoxic chemical backbone of camsirubicin and the
potent broad-spectrum antitumor activity of doxorubicin. Further,
preclinical evidence suggests that this new family of 2-pyrrilino
camsirubicin analogs could be active in doxorubicin-resistant tumor
cells which may enable use in cancer types beyond those possible
with camsirubicin.
In February 2021, we
announced the first patient dosed in our Phase 2b/3 VOICE trial of
Validive® for the
prevention of CRT-induced severe
oral
mucositis in patients with
oropharyngeal cancer
(“VOICE”).
Given the COVID-19 pandemic
and its effects on clinical trials, we have adjusted our clinical
development plans accordingly to fit what is feasible in the
current environment. We have simplified the design of the
previously planned Phase 3 clinical trial for our lead product
candidate, Validive, to a seamless design Phase 2b/3 clinical trial
(our VOICE trial) that will allow us to minimize touch points with
patients and sites. This seamless design will allow us to
immediately advance to the Phase 3 portion of the trial if
supported by the interim data at the end of the Phase 2b portion of
the trial. To complete the VOICE clinical program, including, if
required, completing a smaller second Phase 3 confirmatory clinical
trial, we will require additional funding in the millions or tens
of millions of dollars (depending on if we have consummated a
collaboration or partnership or neither for Validive), which we are
planning to pursue within the next 12 months.
Along with our VOICE trial,
we continue to prioritize supporting the camsirubicin Phase 2
clinical trial for which we signed a collaboration agreement in
June 2019 with Grupo Español de Investigación en Sarcomas
(“GEIS”), discussed in further detail below. We believe
we have funds sufficient to obtain topline results from the run-in
portion of the trial.
In February 2021, we also
announced the publication of a peer-reviewed study in the
European Journal of Cancer
which shows the potential utility of MNPR-101 conjugates as uPAR
imaging agents to improve surgical outcomes in bladder cancer and
for surveillance post-resection. This publication builds on
previous studies using conjugates of MNPR-101 and its mouse analog,
ATN-658, for the optical imaging of oral and colon
cancer.
Our Product Pipeline
58
Our Product Candidates
Validive (clonidine mucobuccal tablet; clonidine MBT)
Validive is a mucobuccal
tablet (MBT) formulation of clonidine. The MBT formulation was
developed to enhance the oral mucosal drug delivery and
significantly increase the salivary concentrations of the active
ingredient while minimizing systemic absorption. The Validive
tablet is tasteless and self-administered once daily by affixing it
to the outside of the patient’s upper gum where it dissolves
slowly over the period of several hours, resulting in the extended
release of clonidine into the oral cavity and oropharynx, the site
of SOM following chemoradiation treatment (“CRT”) for
OPC. Validive therapy is designed to begin on the first day of CRT
and continue daily through the last day of CRT.
SOM is a painful and
debilitating inflammation and ulceration of the mucous membranes
lining the oral cavity and oropharynx in response to chemoradiation
therapy. Patients receiving CRT to treat their OPC often develop
SOM, which remains one of the most common and devastating side
effects of treatment in this indication. We believe Validive has
the potential to address several critical elements that affect SOM
patients, including:
Reduction in the incidence of SOM. SOM
can increase the risk of acute and chronic comorbidities, including
dysphagia, trismus and lung complications, which are often
irreversible and lead to increased hospitalization and the need for
additional interventions. In a Phase 2 clinical trial, the OPC
patient cohort treated with Validive 100 μg demonstrated a
reduction in the absolute incidence of SOM compared to placebo of
26.3% (incidence rate of 65.2% in placebo, 45.0% in Validive 50
μg group, 38.9% in Validive 100 μg group). A reduced
incidence of SOM in OPC patients may lower the risk of acute and
chronic comorbidities and improve quality of life.
Delay in the time to onset of SOM. SOM
can cause cancer treatment delay and/or discontinuation, which may
impact overall survival outcomes. In the Phase 2 clinical trial,
OPC patients had a time to onset of SOM of 37 days in the placebo
cohort; 45-day time to onset of SOM in the Validive 50 μg
cohort; and median was not reached in the Validive 100 μg
group as fewer than half of the patients developed SOM. Prolonging
time to onset of SOM may lead to fewer missed CRT treatments,
resulting in improved overall survival outcomes.
Decrease in the duration of SOM. Longer
duration of SOM leads to a higher risk of the need for parenteral
nutrition and lower quality of life. SOM patients experience
difficulty or inability to drink and/or eat, and difficulty in
swallowing often results in malnourishment and feeding tube
intervention. The Phase 2 clinical trial data demonstrated a
15.5-day reduction (by 37.8%) in the duration of SOM for patients
treated with Validive 100 μg (41 day median duration with
placebo, 34 days with the Validive 50 μg group, and 25.5 days
for the Validive 100 μg group) in patients that developed SOM.
Median duration across all patients, inclusive of both those that
did and did not develop SOM, was 17 days in the placebo group and 0
days in each of the Validive 50 and 100 μg groups. Reduced
duration of SOM may result in lower risk of malnourishment and
feeding tube intervention, and fewer treatment
terminations/delays.
In September 2017, we
exercised an option to license Validive from Onxeo S.A., the
company that had developed Validive through its Phase 2 clinical
trial. In this completed Phase 2 clinical trial, Validive
demonstrated clinically meaningful and dose-dependent efficacy
signals within the 64-patient OPC population randomized to placebo.
Additionally, patients in the Validive cohorts in the Phase 2
clinical trial demonstrated a safety profile similar to that of
placebo. While not designed by us, Onxeo’s promising
preclinical studies and Phase 2 clinical trial have informed the
design and conduct of what we believe will be an effective Phase
2b/3 (VOICE) clinical trial.
SOM typically arises in the
immune tissue at the back of the tongue and throat, which comprise
the oropharynx, and consists of acute severe tissue damage and pain
that prevents patients from swallowing, eating and drinking.
Validive stimulates the alpha-2 adrenergic receptor (alpha-2AR) on
macrophages (white blood cells present in the immune tissues of the
oropharynx) suppressing pro-inflammatory cytokine expression.
Validive exerts its effects locally in the oral cavity and
oropharynx over a prolonged period of time through its unique MBT
formulation. Patients who develop SOM are also at increased risk of
developing late-onset toxicities, including trismus (jaw, neck, and
throat spasms), dysphagia, and lung complications, which are often
irreversible and lead to increased hospitalization and the need for
further interventions sometimes years after completion of CRT. We
believe that a reduction in the incidence and duration of SOM by
Validive will have the potential to reduce treatment
discontinuation and/or treatment delays potentially leading to
improved survival outcomes, and reducing or eliminating long-term
morbidities resulting from CRT.
59
The OPC target population for
Validive is the most rapidly growing segment of head and neck
cancer (“HNC”) patients, estimated to exceed 40,000 new
cases annually of OPC in the U.S alone. The growth in OPC is driven
by the increasing prevalence of oral human papilloma virus
(“HPV”) infections in the U.S. and around the world.
Despite the availability of a pediatric/adolescent HPV vaccine, the
rate of OPC incidence in adults is not anticipated to be materially
reduced for decades due to low adoption of the vaccine to date. As
a result, the incidence of HPV-driven OPC is projected to increase
for many years to come and will continue to support a clinical need
for Validive for the prevention of CRT-induced SOM in patients with
OPC since CRT is the standard of care treatment, and we do not
anticipate this changing for years to come.
A pre-Phase 3 meeting with
the FDA was held, and based on the meeting discussion a Phase 3
clinical protocol and accompanying statistical analysis plan
(“SAP”) was submitted to the FDA for review and
comments. We have also received protocol assistance and advice on
our Phase 3 protocol and SAP from the European Medicines Agency
Committee on Human Medicinal Products (EMA/CHMP/SAWP). Based on
comments and guidance provided by FDA and EMA, and our analysis of
the current COVID-19 pandemic and its effects on clinical trials,
we have modified our original adaptive design Phase 3 clinical
trial to be a seamless Phase 2b/3 (VOICE) clinical trial to better
fit the current clinical research environment. The primary
endpoint, absolute incidence of SOM, remains the same, but the
overall design of the trial has been simplified and the touch
points with the healthcare system have been minimized. We have now
initiated clinical trial sites and commenced dosing in the Phase 2b
portion of our VOICE trial. We anticipate the interim (completion
of Phase 2b portion of the VOICE trial) will be reached in the
first quarter of 2022, and the Phase 3 enrollment will be completed
in the fourth quarter of 2022. Initiating the Phase 3 portion of
the VOICE trial will be subject to the interim (Phase 2b) results.
We will need to raise additional funding or find a suitable
pharmaceutical partner to complete the VOICE clinical program
including, if required, completing a smaller second Phase 3
confirmatory clinical trial. Validive has been granted fast track
designation in the U.S., orphan drug designation in the EU, and has
global intellectual property patent protection through mid-2029 not
accounting for possible extensions.
Camsirubicin (5-imino-13-deoxydoxorubicin; formerly MNPR-201,
GPX-150)
Camsirubicin is a proprietary doxorubicin
analog that is selective for topoisomerase II-alpha. Doxorubicin is
widely used to treat adult and pediatric solid and blood
(hematologic) cancers, including soft tissue sarcomas, breast,
gastric, ovarian and bladder cancers, leukemias and lymphomas.
Despite clinical studies demonstrating the anti-cancer benefit of
higher cumulative doses of doxorubicin, the clinical efficacy of
doxorubicin has historically been limited by the risk of patients
developing irreversible, potentially life-threatening
cardiotoxicity. For example, several clinical studies completed in
the 1990s demonstrated that concurrent doxorubicin (60
mg/m2,
8 cycles) and paclitaxel gave a 94% overall response rate in
patients with metastatic breast cancer but led to 18% of these
patients developing congestive heart failure. Reduction of
doxorubicin to 4-6 cycles of treatment decreased the incidence of
congestive heart failure, but also reduced response rates to
45-55%. In a clinical study looking at dose response, sarcoma
patients on the high dose (75 mg/m2)
doxorubicin had a response rate of 37% compared to just 18% in the
low dose (45 mg/m2)
doxorubicin group. With the cumulative dose restriction on
doxorubicin, the median progression free survival for ASTS patients
is approximately 6 months, with median overall survival of 12-15
months. There is a significant unmet opportunity to develop a
replacement for doxorubicin that can be dosed higher and for
longer.
Camsirubicin has been
engineered specifically to retain the anticancer activity of
doxorubicin while minimizing the toxic effects on the heart.
Similar to doxorubicin, the antitumor effects of camsirubicin are
mediated through the stabilization of the topoisomerase II complex
after a DNA strand break and DNA intercalation leading to tumor
cell apoptosis (cell death). Inhibiting the topoisomerase II-alpha
isoform is desired for the anti-cancer effect, while inhibiting the
topoisomerase II-beta isoform has been demonstrated to mediate, at
least in part, the cardiotoxicity associated with doxorubicin.
Camsirubicin is more selective than doxorubicin for inhibiting
topoisomerase II-alpha versus topoisomerase II-beta. This
selectivity may at least partly explain the minimal cardiotoxicity
that has been observed for camsirubicin in preclinical and clinical
studies to date. We believe these attributes provide a strong
rationale to develop camsirubicin without restriction on cumulative
dose, in a broad spectrum of cancer types.
A Phase 2 clinical trial for
camsirubicin has been completed in patients with advanced (e.g.
unresectable or metastatic) soft tissue sarcoma
(“ASTS”). Median progression free survival for ASTS
patients is approximately 6 months and average life expectancy for
these patients is 12-15 months. In this study, 52.6% of patients
evaluable for tumor progression demonstrated clinical benefit
(partial response or stable disease), which was proportional to
dose and consistently observed at higher cumulative doses of
camsirubicin (>1000 mg/m2). Camsirubicin was very well tolerated
in this study and underscored the ability to potentially administer
camsirubicin without restriction of cumulative dose in patients
with ASTS. Although doxorubicin has been the standard of care
treatment for over 40 years for patients with ASTS, doxorubicin is
limited to a lifetime cumulative dose maximum of 450 mg/m2. This
means that even if a patient is responding, they are pulled off of
doxorubicin treatment once this cumulative dose has been reached.
Thus, there is a significant unmet opportunity to develop a
replacement for doxorubicin that retains anti-cancer activity while
reducing or eliminating the risk for irreversible heart
damage.
60
Based on encouraging clinical
results to date, we plan to continue the development of
camsirubicin as first-line treatment in patients with ASTS, where
the current first-line treatment is doxorubicin. The aim is to
administer camsirubicin without restricting cumulative dose,
thereby potentially improving efficacy beyond that of doxorubicin
by continuing to treat patients who are responding on treatment. In
June 2019, we entered into a clinical collaboration with GEIS. GEIS
will lead a multi-country, randomized, open-label Phase 2 clinical
trial evaluating camsirubicin head-to-head against doxorubicin in
patients with ASTS. GEIS is an internationally renowned non-profit
organization focused on the research, development and management of
clinical trials for sarcoma that has worked with many of the
leading biotech and global pharmaceutical companies. Enrollment of
the trial is currently anticipated to begin in the second quarter
of 2021, and to include approximately 170 ASTS patients, an interim
analysis, and take around two years to enroll. The trial will begin
with a dose escalation (“run-in”) prior to the
randomization portion of the trial. The primary endpoint of the
trial will be progression-free survival, with secondary endpoints
including overall survival, response rate and incidence of
treatment-emergent adverse events. Camsirubicin has been granted
orphan drug designation for the treatment of soft tissue sarcoma in
the U.S. and EU.
MNPR-101 (formerly huATN-658)
MNPR-101 is a novel,
preclinical stage drug candidate. It is a first-in-class humanized
monoclonal antibody to the urokinase plasminogen activator receptor
(“uPAR”), a well-credentialed cancer therapeutic
target. uPAR is a protein receptor that resides on the cell surface
and is overexpressed in many deadly cancers, but has little to no
expression in healthy tissue; several Phase 1 imaging studies in
human advanced cancer patients show that uPAR is detected
selectively in the tumor.
In normal cells, uPAR is
transiently expressed as part of a highly regulated process
required for the breakdown of the extracellular matrix during
normal tissue remodeling. In cancer, however, uPAR is
constitutively overexpressed by the tumor cell, and the uPAR
extracellular matrix degrading function is hijacked by the tumor to
support tissue invasion, metastasis, and angiogenesis. uPAR
expression is important to tumor cell survival, and uPAR expression
increases in high grade and metastatic disease.
MNPR-101 has demonstrated
significant antitumor activity in numerous preclinical models of
tumor growth, both as a monotherapy and in combination with other
therapeutics and is being advanced toward an IND. Based on the
selective expression of uPAR in numerous tumor types, we anticipate
MNPR-101 will be well-tolerated and amenable to a variety of
combination treatment approaches in the clinic.
uPRIT as a Potential Therapeutic for Severe COVID-19
MNPR-101 is also being
developed for the treatment of severe COVID-19 and other
respiratory diseases. We have entered into a collaboration
development agreement with NorthStar to develop potential uPRITs to
treat severe COVID-19. This collaboration combines
NorthStar’s expertise in the innovative production, supply,
and distribution of important medical radioisotopes with our
expertise in therapeutic drug development. NorthStar and we have
coupled MNPR-101 with a therapeutic radioisotope. uPAR seems to be
selectively expressed on aberrantly activated immune cells. In
response to coronavirus infection, these rogue immune cells produce
pro-inflammatory cytokines that can cause runaway inflammation
throughout the body, commonly referred to as a “cytokine
storm.” It is this systemic hyper-inflammatory state that is
thought to be largely responsible for the severe lung injury and
further multiple organ damage that contributes to poor outcomes and
death in patients with severe COVID-19.
In collaboration with NorthStar, we have filed a
provisional patent application entitled “Precision
Radioimmunotherapeutic Targeting of the Urokinase Plasminogen
Activator Receptor (uPAR) for Treatment of Severe COVID-19
Disease” with the U.S. Patent and Trademark Office
(“USPTO”). This application covers novel compositions
and uses of cytotoxic radioisotopes attached to antibodies that
bind to uPAR, thereby creating precision targeted
radiotherapeutics, also known as uPRITs, for the treatment of
severe COVID-19 and other respiratory diseases. Advanced COVID-19
patients frequently develop severe, life-threatening, pulmonary
inflammation as a result of a viral induced cytokine storm. The
development of this cytokine storm is associated with a high rate
of mortality in severe COVID-19 patients, even when oxygen support
and mechanical ventilation are utilized. uPRITs have been designed
with the goal of selectively eradicating the aberrantly activated
immune cells responsible for causing cytokine storm and its harmful
systemic effects. The co-inventors of the provisional patent
application are James Harvey, Chief Scientific Officer of
NorthStar, and Andrew P. Mazar, our Chief Scientific Officer. We
have also entered into collaborations with: IsoTherapeutics
Group, LLC, which generated the uPRIT candidates; Aragen Bioscience
Inc., which screened the uPRIT candidates through preclinical
biochemical testing; and Texas Lung Injury Institute / University
of Texas Health Science Center at Tyler, which plans to perform
preclinical testing and, if successful, clinical
testing.
61
ATN-658 as a Potential Diagnostic for Severe COVID-19
A prototype enzyme-linked
immunosorbent assay (“ELISA”) for measuring blood suPAR
levels using the non-humanized version of MNPR-101 (ATN-658) has
been developed, and we are in discussions with several parties to
further develop and commercialize a suPAR-based test in COVID-19
patients.
The use of suPAR for triaging
COVID-19 patients is supported by a growing body of recent studies.
Rovina et al. 2020 showed that patients with elevated levels of
suPAR at the time of hospital admission are 17 times more likely to
develop severe respiratory failure (p=.0000000012); Arnold et al.
2020 showed suPAR to have the best performance in predicting
outcome (such as intensive care unit admission and death) of all
the biomarkers examined; and Eugen-Olsen et al. 2020 showed that
low levels of suPAR are predictive of mild outcome in COVID-19
patients.
MNPR-101 as a Potential Imaging Agent
Using MNPR-101, a multimodal
imaging probe was developed and tested in vivo in human bladder cancer models.
A publication in the European
Journal of Cancer (Baart et al. 2021) reported that high
expression of uPAR in bladder cancer is localized at the tumor
periphery, suggesting that using a fluorescent-conjugated MNPR-101
probe might allow surgeons to better visualize the borders of the
tumor, potentially resulting in more complete tumor resection and
thereby minimizing relapse. Similar approaches have been utilized
successfully in the resection of other tumor types, such as breast
cancer.
Bladder cancer is often
treated with transurethral resection to remove cancerous tissue;
however, recurrence can occur in up to 78% of patients within 5
years. Up to 40% of recurrent cases develop muscle invasive
disease, which has a poor prognosis and requires complete removal
of the bladder. Many patients with muscle-invasive bladder cancer
go on to develop and succumb to metastatic disease.
Our Strategy
Our management team has
extensive experience in developing therapeutics through regulatory
approval and commercialization. In aggregate, companies they
co-founded have achieved four drug approvals in the U.S. and the
EU, successfully sold an asset developed by management which is
currently in Phase 3 clinical trials, and completed the sale of a
biopharmaceutical company for over $800 million in cash.
Understanding the preclinical, clinical, regulatory and commercial
development processes and hurdles are key factors in successful
drug development and the expertise demonstrated by our management
team across all of these areas increases the probability of success
in advancing the product candidates in our product pipeline. Our
strategic goal is to acquire, develop and commercialize promising
oncology product candidates that address important unmet medical
needs of cancer patients. The six key elements of our strategy to
achieve this goal are to:
●
Leverage data generated from the Phase 2
Validive clinical trial to position us effectively for a successful
VOICE clinical program for Validive for SOM in OPC. In the
Phase 2 clinical trial the absolute incidence of SOM in OPC
patients was reduced by 26.3%, the time to onset was delayed, and
the duration of disease in patients that developed SOM was
decreased by 15.5 days in the Validive 100 μg cohort versus
placebo. In addition to the data from the Phase 2 clinical trial,
we believe the guidance from our key opinion leaders
(“KOLs”) as well as from the FDA and EMA, and our own
internal clinical trial design expertise, position us well for an
effective VOICE clinical trial program.
●
Obtain FDA approval of Validive and maximize
the commercial potential of Validive in the U.S. and the EU,
seeking partnerships outside these markets. If the VOICE
clinical program of Validive is successful and FDA approval is
obtained, we currently intend to commercialize Validive in the U.S.
and the EU ourselves, which may include establishing our own
specialty sales force and seeking partnerships outside of these
territories for regulatory approval and drug sales and
distribution.
●
Advance the clinical development of
camsirubicin, by pursuing clinical indications where doxorubicin
has demonstrated efficacy. ASTS will be the first
indication, which will allow camsirubicin to go head-to-head
against doxorubicin, the current first-line treatment. In this
indication, camsirubicin previously demonstrated clinical benefit
(stable disease or partial response) in 52.6% of patients evaluable
for tumor progression in a single-arm Phase 2 study. Clinical
benefit was proportional to dose and consistently observed at
higher cumulative doses of camsirubicin (>1000 mg/m2). Camsirubicin was very well tolerated
in this Phase 2 study and underscored the ability to potentially
administer camsirubicin without restriction as to cumulative dose
(doxorubicin is limited to 450 mg/m2 cumulative dose due to heart
toxicity).
●
Continue the development of MNPR-101 and
related molecules as a therapeutic, a diagnostic and imaging
agents. We plan to continue the development of MNPR-101 for
diagnostic and therapeutic use in severe COVID-19 and in
cancer.
●
Expand our drug development pipeline through
advancing current assets, in-license and acquisition of oncology
product candidates. The 2-pyrrilino camsirubicin analogs
represent proprietary compositions of matter that retain the
non-cardiotoxic backbone of camsirubicin but may have features in
terms of antitumor activity and mechanism that distinguish this
family of compounds from camsirubicin. We plan to continue the
expansion of our drug development pipeline through acquiring or
in-licensing additional oncology product candidates, particularly
those that leverage existing scientific and clinical data that
helps reduce the risks of the next steps in clinical
development.
●
Utilize the expertise and prior experience of
our team in the areas of asset acquisition, drug development and
commercialization to establish ourselves as a leading
biopharmaceutical company. Our senior executive team has
relevant experience in biopharmaceutical in-licensing and
acquisitions as well as developing product candidates through
approval and commercialization. In aggregate, our team has
co-founded BioMarin Pharmaceutical (Nasdaq: BMRN), Raptor
Pharmaceuticals ($800 million sale to Horizon Pharma), and Tactic
Pharma, LLC (“Tactic Pharma”) (sale of lead asset,
choline tetrathiomolybdate, which was ultimately acquired by
Alexion in June 2018 for $764 million; Alexion is currently in the
process of being acquired by AstraZeneca).
62
Risks Associated with our Business
Our business is subject to
numerous risks and uncertainties, including those highlighted in
“Item 1A - Risk Factors”. These risks include, among
others, the following:
●
We are a clinical
stage biopharmaceutical company with a history of financial losses.
We expect to continue to incur significant losses for the