MONOPAR THERAPEUTICS INC. You should read the following discussion and analysis of our financial condition and results of operations together with our condensed consolidated financial statements and related notes contained in this Quarterly Report on Form 10-Q. Some of the information contained in this discussion and analysis are set forth elsewhere in this Quarterly Report on Form 10-Q, 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. Overview We are a clinical stage biopharmaceutical company 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. Validive Clinical Update
InFebruary 2021 , we dosed the first patient in our Phase 2b/3 VOICE trial of Validive® for the prevention of chemoradiation treatment ("CRT")-induced severe oral mucositis in patients with oropharyngeal cancer ("VOICE"). InAugust 2021 , we successfully reached our target of 20 activated clinical trial sites for the Phase 2b portion of the 2b/3 Validive® VOICE trial and inSeptember 2021 , we received authorization to proceed with the VOICE clinical trial in multiple countries inEurope . We plan to continue to activate additional sites in both the US and the EU. 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, adaptive Phase 2b/3 clinical trial design (our VOICE trial) that will allow us to minimize touch points with patients and sites. This trial 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 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. Camsirubicin Clinical Update InAugust 2021 , we announced clearance from theU.S. Food and Drug Administration ("FDA") to proceed with an open-label Phase 1b dose-escalation clinical trial evaluating camsirubicin plus growth factor support (pegfilgrastim/G-CSF) in patients with advanced soft tissue sarcoma ("ASTS"). InSeptember 2021 we initiated the Phase 1b clinical trial, and inOctober 2021 we dosed the first patients. Following completion of the Phase 1b clinical trial, we continue to expect that Grupo Español de Investigación en Sarcomas ("GEIS") will sponsor and lead a multi-country, randomized, open-label Phase 2 clinical trial to evaluate camsirubicin head-to-head against doxorubicin, the current first-line treatment for ASTS. We believe we have funds sufficient to obtain topline results from the Phase 1b clinical trial. Additional funding will be required to support further development beyond our Phase 1b clinical trial.
Financial Status Under our Capital on DemandTM Sales Agreement withJonesTrading Institutional Services, LLC ("JonesTrading"), throughSeptember 30, 2021 , we sold 1,964,724 shares of our common stock at an average gross price of$10.02 per share for net proceeds of$19,100,602 , after fees and commissions of$591,188 . We did not sell any shares of our common stock under this agreement during the three months endedSeptember 30, 2021 . The maximum aggregate offering price under the agreement has been reached and we do not expect further sales under this agreement. The balance of cash and cash equivalents as ofSeptember 30, 2021 , was$22,341,564 .
MNPR-101 RIT Development Update
Pursuant to our 50/50 collaboration development agreement withNorthStar Medical Radioisotopes, LLC ("NorthStar") to develop potential radioimmunotherapeutics ("RITs") to treat severe COVID-19 (patients with SARS-CoV-2 infection), we have coupled MNPR-101 to therapeutic radioisotopes supplied byNorthStar . The resulting conjugates are designed to be 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 therapeutic goal is to spare healthy cells while quickly reducing the cytokine storm and its harmful systemic effects. ThroughOctober 31, 2021 , we have filed several patent applications on discoveries made through theNorthStar collaboration, and have incurred immaterial expense related to the 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; andTexas Lung Injury Institute /University of Texas Health Science Center at Tyler , which plans to perform preclinical testing and, if successful, clinical testing. In addition, Monopar andNorthStar have advanced their collaboration to investigate MNPR-101 coupled to diagnostic radioisotopes as a companion diagnostic for uPRIT for use in COVID-19 and advanced cancers. 22 Table of Contents
InFebruary 2021 , we announced the publication of a peer-reviewed study in theEuropean Journal of Cancer which reported 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. InMarch 2021 , we announced the publication of a peer-reviewed study titled "Engineered Antibody Fragment against the Urokinase Plasminogen Activator for Fast Delineation of Triple-Negative Breast Cancer by Positron Emission Tomography." Urokinase plasminogen activator ("uPA") is an established biomarker in current breast cancer clinical practice guidelines and its presence is used to select appropriate drug treatment. This study demonstrates the potential to identify breast cancers with uPA overexpression and monitor uPA activity during treatment using positron emission tomography or PET imaging along with our uPA antibody fragment radiotracer. We have a panel of proprietary antibodies and antibody fragments to uPA and its receptor uPAR (such as MNPR-101).
MNPR-202 and Related Analogs Updates
InJune 2021 , we entered into a collaboration agreement with theCancer Science Institute of Singapore ("CSI Singapore"), one ofAsia's premier cancer research centers, at theNational University of Singapore ("NUS") (consistently ranked as one of the world's top universities) to evaluate the activity of MNPR-202 and related analogs in multiple types of cancer. MNPR-202 was designed to retain the same potentially non-cardiotoxic backbone as camsirubicin but is modified at other positions which may enable it to work in certain cancers that are resistant to camsirubicin and doxorubicin. InDecember 2020 , we announced the issuance of our composition of matterU.S. patent (US10,450,340) covering MNPR-202 and related analogs. CSI Singapore will explore the mechanism of action of MNPR-202 and related analogs in preclinical cancer models in order to guide the rational design of MNPR-202 drug combinations including immunotherapy-MNPR-202 for the treatment of cancer. Patent Updates InMay 2021 , we andNorthStar filed a provisional patent application with theU.S. Patent and Trademark Office ("USPTO") titled "Bio-Targeted Radiopharmaceutical Compositions Containing Ac-225 and Methods of Preparation." Radiopharmaceutical therapy is a promising approach to treat cancer and other diseases using radioactive metals bound with proteins/antibodies to target and kill cells. Actinium-225 ("Ac-225") is emerging as a radioactive isotope of choice for radiopharmaceuticals due to favorable properties such as its long half-life, high potency, and induction of localized cell death. This provisional patent relates to the unexpected observation by us andNorthStar that using the metal binding agent 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-3,6,9-triacetic acid ("PCTA") to attach Ac-225 to MNPR-101 resulted in nearly 100% binding of Ac-225 to the PCTA-MNPR-101 conjugates. If validated through further evaluation, it could potentially improve efficacy and safety and enhance manufacturing efficiency of Actinium-based radiopharmaceuticals, the full potential of which are presently constrained by the price and scarcity of Ac-225. Also inMay 2021 , we andNorthStar filed a provisional composition of matter patent application titled "Urokinase Plasminogen Activator Receptor-Targeted Radiopharmaceutical" covering a radiotherapeutic consisting of our proprietary antibody MNPR-101 bound to Ac-225 via the metal binding agent PCTA. This RIT demonstrated 98% radiochemical purity and high stability and has the potential to be a highly selective, potent treatment for a variety of cancers, severe COVID-19, and other diseases characterized by aberrant uPA receptor expression. 23 Table of Contents Our Product Pipeline [[Image Removed: mnpr_10qimg10.jpg]]
Our Product Candidates
Validive (clonidine hydrochloride mucobuccal tablet; clonidine HCI MBT)
Validive is a mucobuccal tablet ("MBT") formulation of clonidine. The MBT
formulation was developed to enhance oral mucosal drug delivery and provide high
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 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 severe oral mucositis ("SOM") following
chemoradiation treatment ("CRT") for oropharyngeal cancer ("OPC"). Validive
therapy is designed to begin on the first day of CRT and continue daily through
the last day of CRT.
SOM is the painful and debilitating inflammation and ulceration of the mucous
membranes lining the oral cavity and oropharynx in response to chemoradiation
therapy. The majority of patients receiving CRT to treat their OPC develop SOM,
which is 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, improve clinical outcomes and 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 ug and
100 µg groups. Reduced duration of SOM may result in lower risk of
malnourishment and feeding tube intervention, and fewer treatment
terminations/delays.
24
Table of Contents
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 (disruption of a patient's ability to eat and drink due to
difficulty in swallowing), 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.
The OPC target population for Validive is the most rapidly growing segment of
head and neck cancer ("HNC") patients, estimated to be above 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 half of 2022, and the Phase 3 enrollment will be completed
in the first half of 2023. We will need to raise additional funding or find a
suitable pharmaceutical partner to complete the VOICE clinical program
including, if required, completion of a 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. 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 at higher cumulative doses of drug. 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.
25
Table of Contents
A Phase 2 clinical trial for camsirubicin has been completed in patients with
ASTS. 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.
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 to treatment.
In June 2019 , we executed a clinical collaboration agreement with GEIS for the
development of camsirubicin 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. Based on our inability to
gain timely regulatory approval to initiate the planned camsirubicin
dose-escalation run-in and Phase 2 clinical trial in Spain , we submitted an IND
with the FDA and gained clearance to conduct a Phase 1b dose escalation clinical
trial in ASTS patients in the U.S. In September 2021 we initiated the Phase 1b
clinical trial in the U.S. , and in October 2021 we dosed the first patient.
Following completion of the Phase 1b clinical trial, we continue to expect that
GEIS will sponsor and lead a multi-country, randomized, open-label Phase 2
clinical trial to evaluate camsirubicin head-to-head against doxorubicin, the
current first-line treatment for ASTS. We believe we have funds sufficient to
obtain topline results from the Phase 1b clinical trial. Additional funding will
be required to support further development beyond the Phase 1b clinical trial.
Camsirubicin has been granted orphan drug designation for the treatment of soft
tissue sarcoma in the U.S. and the 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 utilizing a peptide against uPAR in 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. 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.
26
Table of Contents
uPRIT as a Potential Therapeutic for Severe COVID-19
A radioimmunotherapeutic ("RIT") based on MNPR-101 is being developed for the
treatment of severe COVID-19 and cancer. 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. We have coupled MNPR-101 with a
therapeutic radioisotope in collaboration with NorthStar and IsoTherapeutics
Group, LLC , which have generated the MNPR-101 RIT conjugates. uPAR seems to be
selectively expressed on aberrantly activated immune cells. In response to
coronavirus (SARS-CoV2) 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 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 USPTO on June 15, 2020 . A full international application (International
Application Number PCT/US2021/037416) that claims priority to the provisional
filing date was filed under the Patent Cooperation Treaty ("PCT") on June 15,
2021 . 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.
In May 2021 , we and NorthStar filed a provisional patent application with the
USPTO titled "Bio-Targeted Radiopharmaceutical Compositions Containing Ac-225
and Methods of Preparation." Radiopharmaceutical therapy is a promising approach
to treat cancer and other diseases using radioactive metals bound with
proteins/antibodies to target and kill cells. If validated through further
evaluation, it could potentially improve efficacy and safety and enhance
manufacturing efficiency of Actinium-based radiopharmaceuticals, the full
potential of which are presently constrained by the price and scarcity of
Ac-225.
Also, the provisional composition of matter patent application titled "Urokinase
Plasminogen Activator Receptor-Targeted Radiopharmaceutical" covering a
radiotherapeutic consisting of our proprietary antibody MNPR-101 bound to Ac-225
via the metal binding agent PCTA has the potential to be a highly selective,
potent treatment for a variety of cancers, severe COVID-19, and other diseases
characterized by aberrant uPAR expression.
In addition to NorthStar and the IsoTherapeutics Group, LLC , which generated the
uPRIT candidates, we have entered into collaborations with: 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.
uPRIT as a Potential Therapeutic for Cancer
Monopar is also developing uPRITs, cytotoxic radioisotopes attached to antibodies that bind to uPAR, as precision targeted radioimmunotherapeutics for cancer. uPAR is a protein receptor that resides on the cell surface and is expressed in many deadly cancers, but has little to no expression in healthy tissue. Monopar is conducting preclinical development of uPRITs and companion diagnostics, which consist of imaging radioisotopes attached to antibodies that bind to uPAR, for the potential diagnosis and treatment of advanced cancers.
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. 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. A publication in theEuropean 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. 27 Table of Contents
uPA and its receptor uPAR work together to drive aggressive tumor invasion, leading to metastasis, morbidity, and mortality in breast and other cancers. However, the amount of uPA in tumor is difficult to measure and currently requires a substantial amount of fresh frozen tissue. In a recent peer-reviewed publication, our antibody fragment (ATN-291 F(ab')2) conjugated to a copper radiotracer enabled rapid PET visualization of tumors with uPA overexpression in a human breast cancer model in mice. PET imaging may expand the current application of uPA as a breast cancer biomarker non-invasively without the need to obtain substantial amounts of tumor biopsy tissue and enable the monitoring of tumor uPA levels during treatment. The publication demonstrates, and we may further research, the potential utility of our uPA antibody fragments as imaging agents in breast and other cancers. MNPR-202
MNPR-202 is a camsirubicin analog, designed to retain the same potentially non-cardiotoxic backbone as camsirubicin but is modified at other positions which may enable it to be efficacious in certain cancers that are resistant to camsirubicin and doxorubicin. MNPR-202 and related analogs are covered under a newly issuedU.S. composition of matter patent (US10,450,340).
In collaboration with CSI Singapore, we plan to evaluate the activity of MNPR-202 and related analogs in preclinical models of cancer.
Our Strategy
Our management team has extensive experience in developing therapeutics and medical technologies through global regulatory approval and commercialization. In aggregate, companies they co-founded have achieved four drug approvals and three diagnostic medical imaging device approvals in theU.S. and the EU, successfully sold an asset developed by management which is currently in Phase 3 clinical trials, sold two oncology-focused diagnostic imaging businesses to Fortune Global 1000 firms, and completed the clinical and commercial development and ultimately the sale of a commercial biopharmaceutical company for over$800 million in cash. In addition, the team has supported multiple regulatory submissions with the FDA and EMA and launched multiple drugs in theU.S and the EU. 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. Seven key elements of our strategy to achieve this goal
are to:
· Leverage data generated from the Phase 2 Validive clinical trial to execute 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 SOM 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 and EMA approval of Validive to maximize the commercial potential
of Validive in both the
markets. If the VOICE clinical program of Validive is successful and FDA and
EMA approvals are obtained, we currently intend to commercialize Validive in
the
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 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 was
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 due to heart
toxicity to 450 mg/m2 cumulative dose).
· Continue the development of MNPR-101, MNPR-101 RIT and related molecules as
therapeutic, diagnostic and imaging agents. We plan to continue the
development of MNPR-101, MNPR-101 RIT and related molecules for diagnostic,
imaging, and therapeutic use in severe COVID-19 and in cancer.
· Continue the development of MNPR-202 and related analogs in multiple types of
cancers. The 2-pyrrilino camsirubicin analog (MNPR-202) and related analogs
represent proprietary compositions of matter designed to retain the
non-cardiotoxic backbone of camsirubicin yet exhibit novel features in terms
of antitumor activity and mechanism that distinguish these analogs from
camsirubicin as well as from doxorubicin.
28
Table of Contents
· Expand our drug development pipeline through advancing current assets,
in-licensing, and acquisition of oncology product candidates. 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. Inaggregate, our team has co-founded BioMarin Pharmaceutical (Nasdaq: BMRN),
Olympus),
tetrathiomolybdate, which was ultimately acquired by Alexion in
$764 million ; Alexion was recently acquired by AstraZeneca. Revenues We are an emerging growth company. We have no approved drugs and have not generated any revenues. To date, we have engaged in acquiring or in-licensing pharmaceutical drug product candidates, entering into collaboration agreements for testing and clinical development of our drug product candidates and providing the infrastructure to support the clinical development of our drug product candidates. We do not anticipate commercial revenues from operations until we complete testing and development of one of our drug product candidates and obtain marketing approval or we sell, enter into a collaborative marketing arrangement, or out-license one of our drug product candidates to another party. See "Liquidity and Capital Resources".
Recently Issued and Adopted Accounting Pronouncements
During the three months ended
Critical Accounting Policies and Use of Estimates
While our significant accounting policies are described in more detail in Note 2 of our condensed consolidated financial statements included elsewhere in this Quarterly Report on Form 10-Q, we believe the following accounting policies to be critical to the judgments and estimates used in the preparation of our condensed consolidated financial statements. Clinical Trials Expense
We accrue and expense the costs for clinical trial activities performed by third parties based upon estimates of the percentage of work completed over the life of the individual study in accordance with agreements established with contract research organizations, service providers, and clinical trial sites. We estimate the amounts to accrue based upon discussions with internal clinical personnel and external service providers as to progress or stage of completion of trials or services and the agreed upon fee to be paid for such services. Costs of setting up clinical trial sites for participation in the trials are expensed immediately as R&D expenses. Clinical trial site costs related to patient screening and enrollment are accrued as patients are screened/entered into
the
trial.
Stock-Based Compensation
We account for stock-based compensation arrangements with employees,
non-employee directors and consultants using a fair value method, which requires
the recognition of compensation expense for costs related to all stock-based
awards, including stock option grants and restricted stock units ("RSUs"). The
fair value method requires us to estimate the fair value of stock-based payment
awards on the date of grant using an option pricing model or the closing stock
price on the date of grant in the case of RSUs.
29
Table of Contents
Stock-based compensation costs for stock awards granted to our employees,
non-employee directors and consultants are based on the fair value of the
underlying instruments calculated using the Black-Scholes option-pricing model
on the date of grant for stock options and using the closing stock price on the
date of grant for RSUs and recognized as expense on a straight-line basis over
the requisite service period, which is the vesting period. Determining the
appropriate fair value model and related assumptions requires judgment,
including selecting methods for estimating the Company's future stock price
volatility, forfeiture rates and expected term. The expected volatility rates
are estimated based on the actual volatility of comparable public companies over
recent historical periods of the same length as the expected term. We generally
selected these companies based on reasonably comparable characteristics,
including market capitalization, risk profiles, stage of corporate development
and with historical share price information sufficient to meet the expected term
of the stock-based awards. The expected term for stock options granted during
the three and nine months ended September 30, 2021 , and 2020 was estimated using
the simplified method. Forfeitures are estimated at the time of grant and
revised, if necessary, in subsequent periods if actual forfeitures differ from
those estimates. We have not paid dividends and do not anticipate paying a cash
dividend in future vesting periods and, accordingly, use an expected dividend
yield of zero. The risk-free interest rate is based on the rate of U.S. Treasury
securities with maturities consistent with the estimated expected term of the
awards.
Results of Operations
Comparison of the Three and Nine Months Ended
The following table summarizes the results of our operations for the three and
nine months ended
Three Months Ended September 30 ,
Nine Months Ended
(Unaudited) (Unaudited)
(in thousands) 2021 2020 Variance 2021 2020 Variance
Research and
development
expenses $ 1,827 $ 1,256 $ 571 $ 4,511 $ 2,433 $ 2,078
General and
administrative
expenses 632 392 240 1,935 1,815 120
Total
operating
expenses 2,459 1,648 811 6,446 4,248 2,198
Operating loss (2,459 ) (1,648 ) (811 ) (6,446 ) (4,248 ) (2,198 )
Interest
income 1 9 (8 ) 23 72 (49 )
Net loss $ (2,458 ) $ (1,639 ) $ (819 ) $ (6,423 ) $ (4,176 ) $ (2,247 ) Research and Development Expenses
Research and Development ("R&D") expenses for the three months ended September
30, 2021 , were $1,827,000 , compared to $1,256,000 for the three months ended
September 30, 2020 . This represents an increase of $571,000 primarily attributed
to increases in expenses of $452,000 for Validive clinical trial expenses and
$210,000 due to annual R&D personnel salary increases, annual (non-cash) equity
grants, salaries and benefits of new R&D personnel net of a decrease in CEO's
salary and benefits allocated to R&D expenses and $18,000 in net increases to
other R&D expenses offset by a decrease of $109,000 in camsirubicin regulatory
and manufacturing-related costs.
R&D expenses for the nine months ended September 30, 2021 , were $4,511,000 ,
compared to $2,433,000 for the nine months ended September 30, 2020 . This
represents an increase of $2,078,000 primarily attributed to increases in
expenses of $975,000 for Validive clinical trial expenses, $723,000 due to
annual R&D personnel salary increases, annual (non-cash) equity grants, salaries
and benefits of new R&D personnel and an increase in the CEO's salary and
benefits allocated to R&D expenses due to significant efforts related to the
start-up of clinical trial activities, $303,000 for the planning and initiation
of the camsirubicin Phase 1b clinical trial including regulatory and
manufacturing-related costs, and $77,000 in net increases to other R&D expenses.
General and Administrative Expenses
General and administrative ("G&A") expenses for the three months ended September
30, 2021 , were $632,000 , compared to $392,000 for the three months ended
September 30, 2020 . This represents an increase of $240,000 primarily
attributable to increases in expenses of $201,000 for annual G&A personnel
salary increases, annual (non-cash) equity grants and an increase of the CEO's
salary and benefits allocated to G&A and $43,000 in patent expenses offset by
$4,000 in net decreases to other G&A expenses.
G&A expenses for the nine months ended September 30, 2021 , were $1,935,000 ,
compared to $1,815,000 for the nine months ended September 30, 2020 . This
represents an increase of $120,000 primarily attributed to increases in expenses
of $96,000 for patent expenses, $66,000 for annual G&A personnel salary
increases, annual (non-cash) equity grants offset by a decrease in the CEO's
salary and benefits allocated to G&A, $36,000 for G&A consulting and $7,000 for
net increases to other G&A expenses offset by $85,000 for the reduction in
stock-based compensation for non-employee directors.
30
Table of Contents
Interest Income
Interest income for the three months endedSeptember 30, 2021 , decreased by$8,000 versus the three months endedSeptember 30, 2020 , due to a significant decrease in bank interest rates offset by an increase in bank balances resulting from funds raised in our Capital on DemandTM Sales Agreement with JonesTrading during the first quarter of 2021. Interest income for the nine months endedSeptember 30, 2021 , decreased by$49,000 versus the nine months endedSeptember 30, 2020 , due to a significant decrease in bank interest rates offset by an increase in bank balances resulting from funds raised in our Capital on DemandTM Sales Agreement with JonesTrading during the first quarter of 2021.
Liquidity and Capital Resources
Sources of Liquidity
We have incurred losses and cumulative negative cash flows from operations since our incorporation inDecember 2015 resulting in an accumulated deficit of approximately$38.6 million as ofSeptember 30, 2021 . We anticipate that we will continue to incur losses for the foreseeable future. We expect that our R&D and G&A expenses will increase to enable the execution of our strategic plan. As a result, we anticipate that we will seek to raise additional capital within the next 12 months to fund our future operations. We will seek to obtain needed capital through a combination of equity offerings, debt financings, strategic collaborations and grant funding. To date, we have funded our operations through net proceeds from the initial public offering of our common stock, net proceeds from sales under our Capital on DemandTM Sales Agreement, private placements of our preferred and common stock, and the net receipt of funds related to the acquisition of camsirubicin. We anticipate that the currently available funds as ofOctober 31, 2021 , will fund our obligations throughDecember 31, 2022 .
We invest our cash equivalents in a money market account.
Cash Flows
The following table provides information regarding our cash flows for the nine
months ended
Nine Months
Ended September
Nine Months Ended 30, 2021,
September 30, Compared to
Nine Months
Ended September
(in thousands) 2021 2020 30, 2020Net cash used in operating activities$ (5,285 ) $ (3,421 ) $ (1,864 ) Net cash provided by financing activities 10,887 8,189
2,698
Effect of exchange rates 3 1 2 Net increase in cash and cash equivalents$ 5,605 $ 4,769 $
836
During the nine months ended
31
Table of Contents
Cash Flow Used in Operating Activities
The increase of approximately
Cash Flow Used in Investing Activities
There was no cash flow used in investing activities for the nine months ended
Cash Flow Provided by Financing Activities
The increase in cash flow provided by financing activities during the nine
months ended
Future Funding Requirements To date, we have not generated any revenue from product sales. We do not know when, or if, we will generate any revenue from product sales. We do not expect to generate any revenue from product sales or royalties unless and until we obtain regulatory approval of and commercialize any of our current or future drug product candidates or we out-license or sell a drug product candidate to another party. At the same time, we expect our expenses to increase in connection with our ongoing development activities, particularly as we continue the research, development, future preclinical studies and clinical trials of, and seek regulatory approval for, our current and future drug product candidates. If we obtain regulatory approval of any of our current or future drug product candidates, we will need substantial additional funding for commercialization requirements and our continuing drug product development
operations.
32
Table of Contents
As a company, we have not completed development through marketing approvals of any therapeutic products. We expect to continue to incur significant increases in expenses and increasing operating losses for the foreseeable future. We anticipate that our expenses will increase substantially as we:
· advance the clinical development and execute the regulatory strategy for
Validive;
· advance the clinical development and execute the regulatory strategy for
camsirubicin;
· continue the preclinical activities and potentially enter clinical
development of MNPR-101 and MNPR-101-derived radioimmunotherapeutics and
companion diagnostics, to treat severe COVID-19 (patients with SARS-CoV-2
infection) and cancer;
· continue the preclinical activities, and potentially later-on enter clinical
development, of MNPR-202 (and related analogs) for various cancer
indications;
· acquire and/or license additional pipeline drug product candidates and pursue
the future preclinical and/or clinical development of such drug product
candidates;
· seek regulatory approvals for any of our current and future drug product
candidates that successfully complete registration clinical trials;
· establish or purchase the services of a sales, marketing and distribution
infrastructure to commercialize any products for which we obtain marketing
approval;
· develop or contract for manufacturing/quality capabilities or establish a
reliable, high quality supply chain sufficient to support our clinical
requirements and to provide sufficient capacity to launch and supply the
market for any product for which we obtain marketing approval; and· add or contract for required operational, financial and management
information systems and capabilities and other specialized expert personnel
to support our drug product candidate development and planned
commercialization efforts.
We anticipate that the funds available as of October 31, 2021 , will fund
our obligations through December 2022 . We have based this estimate on
assumptions that may prove to be wrong, and we could use our available capital
resources sooner than we currently expect. Because of the numerous risks and
uncertainties associated with the development and commercialization of our drug
product candidates, and the extent to which we enter into collaborations with
third parties to participate in the development and commercialization of our
drug product candidates, we are unable to accurately estimate with high
reliability the amounts and timing required for increased capital outlays and
operating expenditures associated with our current and anticipated drug product
candidate development programs.
Our future capital requirements will depend on many factors, including:
· the progress of clinical development and regulatory interactions and
approvals of Validive;
· the progress of clinical development and regulatory interactions and
approvals of camsirubicin;
· the progress of preclinical and clinical development of MNPR-101 and
MNPR-101-derived radioimmunotherapeutics and companion diagnostics, to treat
severe COVID-19 (patients with SARS-CoV-2 infection) and cancer, including
activities through our collaboration with
· the progress of preclinical and potentially clinical development of MNPR-202
(and related analogs)
· the number and characteristics of other drug product candidates that we may
license, acquire, invent or otherwise pursue;
· the scope, progress, timing, cost and results of research, preclinical
development and clinical trials of future drug product candidates;
· the costs, timing and outcomes of seeking and obtaining and maintaining FDA
and international regulatory approvals;
33
Table of Contents
· the costs associated with manufacturing/quality requirements and establishing
or contracting for sales, marketing and distribution capabilities;
· our ability to maintain, expand and defend the scope of our intellectual
property portfolio, including the amount and timing of any payments we may be
required to make in connection with the licensing, filing, defense and
enforcement of any patents or other intellectual property rights;
· our need and ability to hire or contract for additional management,
administrative, scientific, medical, sales and marketing, and
manufacturing/quality and other specialized personnel or external expertise;
· the effect and timing of entry of competing products or new therapies that
may limit market penetration or prevent the introduction of our drug product
candidates or reduce the commercial potential of our product portfolio;
· our need to implement additional required internal systems and
infrastructure; and
· the economic and other terms, timing and success of our existing
collaboration and licensing arrangements and any collaboration, licensing or
other arrangements into which we may enter in the future, including the
timing of receipt of or payment to or from others of any milestone or royalty
payments under these arrangements.
Expenditures are expected to increase in the remainder of 2021 and onward for:
· clinical research services and clinical site fees for our VOICE clinical
program, including, if required, completing a second Phase 3 confirmatory
clinical trial;
· process development, manufacturing costs, clinical trial expenses and
clinical database management of camsirubicin in connection with the Phase 1b
dose escalation clinical trial and other future clinical development;
· support of the development of MNPR-101-derived radioimmunotherapeutics and
companion diagnostics to treat severe COVID-19 (patients with SARS-CoV-2
infection) and cancer, including activities through our collaboration with
· preclinical studies (and if successful, clinical studies) of MNPR-101,
MNPR-202 (and related analogs); and
· employee compensation and consulting fees to support our product candidate
programs including Validive, camsirubicin, MNPR-101, MNPR-101 RIT (uPRIT and
related compounds) and companion diagnostics and MNPR-202 (and related
analogs).
We have activated clinical trial sites and are dosing patients in our VOICE clinical trial. In order to complete the VOICE clinical program, including, if required, completing a 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), or find a suitable pharmaceutical partner, both of which we are planning to pursue within the next 12 months. There can be no assurance that any such events will occur. We have also initiated and commenced dosing in our Phase 1b camsirubicin clinical trial. We intend to continue evaluating drug product candidates for the purpose of growing our pipeline. Identifying and securing high-quality compounds usually takes time and related expenses; however, our spending could be significantly accelerated in the remainder of 2021 and onward if additional drug product candidates are acquired and enter clinical development. In this event, we may be required to expand our management team, and pay higher contract manufacturing costs, contract research organization fees, other clinical development costs and insurance costs that are not currently projected. The anticipated operating cost increases in the remainder of 2021 and onward are expected to be primarily driven by the funding of our VOICE clinical program, support of the camsirubicin clinical program, development of MNPR-101, MNPR-101 RIT (uPRIT and related compounds) and companion diagnostics and development of MNPR-202 (and related analogs). Beyond our need to raise additional funding in the coming 12 months to complete the VOICE clinical program, we will also need significant additional funding thereafter in order to commercialize Validive if approved for marketing, support of the camsirubicin clinical program beyond the Phase 1b clinical trial, to support our collaboration withNorthStar , further development of MNPR-101, MNPR-101 RIT (uPRIT and related compounds) and companion diagnostics, further development of MNPR-202 (and related analogs) and generally to support our current and any future product candidates through completion of clinical trials, approval processes and, if applicable, commercialization. 34 Table of Contents
Until we can generate a sufficient amount of product revenue to finance our cash requirements, we expect to finance our future cash needs primarily through a combination of equity offerings, debt financings, strategic collaborations and grant funding. To the extent that we raise additional capital through the sale of equity or convertible debt securities, the ownership interest of our current stockholders will be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect our current stockholders' rights. Debt financing, if available, may involve agreements that include covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making capital expenditures or declaring dividends. If we raise additional funds through marketing and distribution arrangements or other collaborations, strategic alliances or licensing arrangements with other parties, we likely will have to relinquish valuable rights to our technologies, future revenue streams, research programs or drug product candidates or grant licenses on terms that may not be favorable to us, which will reduce our future returns and affect our future operating flexibility. If we are unable to raise additional funds through equity or debt financings when needed, we may be required to delay, limit, reduce or terminate our pipeline product development or commercialization efforts or grant rights to others to develop and market drug product candidates that we would otherwise prefer to develop and market ourselves.
Contractual Obligations and Commitments
License, Development and Collaboration Agreements
Onxeo S.A. InJune 2016 , we executed an agreement with Onxeo S.A., a French public company, which gave us the exclusive option to license (on a world-wide exclusive basis) Validive (clonidine hydrochloride mucobuccal tablet; clonidine HCI MBT a mucoadhesive tablet of clonidine based on the Lauriad mucoadhesive technology). The agreement includes clinical, regulatory, developmental and sales milestones that could reach up to$108 million if we achieve all milestones, and escalating royalties from 5% to 10% on net sales. InSeptember 2017 , we exercised the option to license Validive from Onxeo for$1 million , but as ofOctober 31, 2021 , we have not been required to pay Onxeo any other funds under the agreement. We anticipate the need to raise significant funds to support the completion of clinical development and marketing approval of Validive. Under the agreement, we are required to pay royalties to Onxeo on a product-by-product and country-by-country basis until the later of (1) the date when a given product is no longer within the scope of a patent claim in the country of sale or manufacture, (2) the expiry of any extended exclusivity period in the relevant country (such as orphan drug exclusivity, pediatric exclusivity, new chemical entity exclusivity, or other exclusivity granted beyond the expiry of the relevant patent), or (3) a specific time period after the first commercial sale of the product in such country. In most countries, including theU.S. , the patent term is generally 20 years from the earliest claimed filing date of a non-provisional patent application in the applicable country, not taking into consideration any potential patent term adjustment that may be filed in the future or any regulatory extensions that may be obtained. The royalty termination provision pursuant to (3) described above is shorter than 20 years and is the least likely cause of termination of royalty payments. The Onxeo license agreement does not have a pre-determined term, but expires on a product-by-product and country-by-country basis; that is, the agreement expires with respect to a given product in a given country whenever our royalty payment obligations with respect to such product have expired. The agreement may also be terminated early for cause if either we or Onxeo materially breach the agreement, or if either we or Onxeo become insolvent. We may also choose to terminate the agreement, either in its entirety or as to a certain product and a certain country, by providing Onxeo with advance notice.
Grupo Español de Investigación en Sarcomas ("GEIS")
InJune 2019 , we executed a clinical collaboration with GEIS for the development of camsirubicin in patients with advanced soft tissue sarcoma ("ASTS"). Following completion of the Phase 1b clinical trial in theU.S. that we initiated in the third quarter of 2021 with the first patient dosed inOctober 2021 , we continue to expect that GEIS will sponsor and lead a multi-country, randomized, open-label Phase 2 clinical trial to evaluate camsirubicin head-to-head against doxorubicin, the current first-line treatment for ASTS. We will provide study drug and supplemental financial support for the clinical trial estimated to average approximately$2 million to$3 million per year. During the three and nine months endedSeptember 30, 2021 , in preparation for the Phase 1b clinical trial, we incurred$0.3 million and$1.0 million , respectively, in expenses including clinical material manufacturing-related costs and database management expenses. During the three and nine months endedSeptember 30, 2020 , we incurred$0.4 million and$0.6 million , respectively, in expenses under the GEIS agreement and other clinical-related expenses including clinical material manufacturing-related costs and database management expenses. We can terminate the agreement by providing GEIS with advance notice, and without affecting our rights and ownership to any intellectual property or
clinical data.XOMA Ltd. Pursuant to a non-exclusive license agreement withXOMA Ltd. for the humanization technology used in the development of MNPR-101, we are obligated to payXOMA Ltd. clinical, regulatory and sales milestones which could reach up to$14.925 million if we achieve all milestones for MNPR-101. The agreement does not require the payment of sales royalties. There can be no assurance that we will achieve any milestones. As ofOctober 31, 2021 , we had not reached any milestones and had not been required to payXOMA Ltd. any funds under this
license agreement.
35
Table of Contents
Service Providers
In the normal course of business, we contract with service providers to assist
in the performance of R&D, including drug product manufacturing, process
development, clinical development, and G&A including financial strategy, audit,
tax and legal support. We can elect to discontinue the work under these
agreements at any time. We could also enter into collaborative research and
development, contract research, manufacturing and supplier agreements in the
future, which may require upfront payments and/or long-term commitments ofcash. Office Lease
We are currently leasing office space in theVillage of Wilmette, Illinois for$4,487 per month on a month-to-month basis, and we anticipate that we will lease additional space in the future as we hire additional personnel. Legal Contingencies
We are currently not, and to date have never been, a party to any adverse material legal proceedings.
Indemnification In the normal course of business, we enter into contracts and agreements that contain a variety of representations and warranties and provide for general indemnification. Our exposure under these agreements is unknown because it involves claims that may be made against us in the future, but that have not yet been made. To date, we have not paid any claims or been required to defend any action related to our indemnification obligations. However, we may record charges in the future as a result of these indemnification obligations. In accordance with our Second Amended and Restated Certificate of Incorporation, Amended and Restated Bylaws and the indemnification agreements entered into with each officer and non-employee director, we have indemnification obligations to our officers and non-employee directors for certain events or occurrences, subject to certain limits, while they are serving at our request in such capacity. There have been no claims to date.
Off-Balance Sheet Arrangements
To date, we have not had any off-balance sheet arrangements, as defined under
the
© Edgar Online, source
