Forward-Looking Statements
This document and the documents incorporated in this document by reference contain forward-looking statements that are subject to risks and uncertainties. All statements other than statements of historical fact contained in this document and the materials accompanying this document are forward-looking statements.
The forward-looking statements are based on the beliefs of our management, as well as assumptions made by and information currently available to our management. Frequently, but not always, forward-looking statements are identified by the use of the future tense and by words such as "believes," expects," "anticipates," "intends," "will," "may," "could," "would," "projects," "continues," "estimates" or similar expressions. Forward-looking statements are not guarantees of future performance and actual results could differ materially from those indicated by the forward-looking statements. Forward-looking statements involve known and unknown risks, uncertainties, and other factors that may cause our or our industry's actual results, levels of activity, performance, or achievements to be materially different from any future results, levels of activity, performance, or achievements expressed or implied by the forward-looking statements.
The forward-looking statements contained or incorporated by reference in this document are forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended ("Securities Act") and Section 21E of the Securities Exchange Act of 1934, as amended ("Exchange Act") and are subject to the safe harbor created by the Private Securities Litigation Reform Act of 1995. These statements include declarations regarding our plans, intentions, beliefs, or current expectations.
Among the important factors that could cause actual results to differ materially
from those indicated by forward-looking statements are the risks and
uncertainties described under "Risk Factors" in our Annual Report and elsewhere
in this document and in our other filings with the
Forward-looking statements are expressly qualified in their entirety by this cautionary statement. The forward-looking statements included in this document are made as of the date of this document and we do not undertake any obligation to update forward-looking statements to reflect new information, subsequent events, or otherwise.
General BUSINESS OVERVIEW
We are a global leader focused on improving the ways scientists use knowledge and data to predict the properties and outcomes of pharmaceutical and biotechnology agents and provide a wide range of early discovery, preclinical, and clinical consulting services and software. Our innovations in integrating new and existing science in medicinal chemistry, computational chemistry, pharmaceutical science, biology, physiology, and machine learning into our software have made us the leading software provider for PBPK modeling and simulation, prediction of molecular properties from structure, and prediction of drugs to induce liver injury or to treat nonalcoholic fatty liver disease.
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We generate revenue by delivering relevant, cost-effective software and creative and insightful consulting services. Pharmaceutical and biotechnology companies use our software programs and scientific consulting services to guide early drug discovery (molecule design and screening), preclinical, and clinical development programs. They also use our software products and services to enhance their understanding of the properties of potential new medicines and to use emerging data to improve formulations, select and justify dosing regimens, support the generics industry, optimize clinical trial designs, and simulate outcomes in special populations, such as the elderly and pediatric patients.
Simulation Plus acquired
PRODUCTS General
We currently offer ten software products for pharmaceutical research and
development: five simulation programs that provide time-dependent results based
on solving large sets of differential equations: GastroPlus®; DDDPlus™;
MembranePlus™; DILIsym®; and NAFLDsym™; three programs that are based on
predicting and analyzing static (not time-dependent) properties of chemicals:
ADMET Predictor®; MedChem Designer™; and MedChem Studio™ (the combination of
ADMET Predictor, MedChem Designer, and
GastroPlus®
Our flagship product, originally introduced in 1998, and currently our largest
single source of software revenue, is GastroPlus. GastroPlus mechanistically
simulates the absorption, pharmacokinetics, pharmacodynamics, and drug-drug
interactions of compounds administered to humans and animals and is currently
the most widely used commercial software of its type by pharmaceutical
companies, the
Because of the widespread use of GastroPlus, we were the only non-European
company invited to join the European Innovative Medicines Initiative (IMI)
program for Oral Bioavailability Tools (OrBiTo). OrBiTo was an international
collaboration among 27 industry, academic, and government organizations working
in the area of oral absorption of pharmaceutical products. Because we are
outside of the
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In
We were awarded another RCA by the FDA in
In
In
In addition to the two active funded efforts with the FDA described above, we
also have two unfunded RCAs with the FDA: one with the
In
In
In
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Our goal with GastroPlus is to integrate the most advanced science into
user-friendly software to enable researchers and regulators to perform
sophisticated analyses of complex compound behaviors in humans and laboratory
animals. Already the most widely used program in the world for PBBM/PBPK
modeling, the addition of these new capabilities is expected to expand the user
base in the early pharmaceutical research and development process, while also
helping us to further penetrate biopharmaceuticals, food, cosmetics, and general
toxicology markets. We work to release updated versions of the program on an
ongoing basis. In
· The ability to add lysosomal trapping effect to PBPK tissues · New mechanistic pregnancy PBPK model (with fetus compartment) · Additional solubility inputs for different drug forms (crystalline, amorphous) · New models of standard compounds (substrates/inhibitors/inducers) in DDI Module · Expanded fed state conditions based on meal type · New ability to allow different tissue model types (perfusion- or permeability-limited) between parent and metabolites or victim perpetrator in metabolite tracking/DDI simulations · PK-PD model additions to PKPlus Module · Updates to the dermal absorption (TCAT) model through Cosmetics Europe project · New effect of immune response with intramuscular injection models · Updated default populations for extensive, intermediate, and poor metabolizers based on specific genotypes DDDPlus™
DDDPlus mechanistically simulates in vitro (laboratory) experiments that measure
the rate of dissolution of a drug as well as, if desired, the additives
(excipients) in a particular dosage form (e.g., powder, tablet, capsule, or
injectable solids) under a variety of experimental conditions. This unique
software program is used by formulation scientists in industry and the FDA to
(1) understand the physical mechanisms affecting the disintegration and
dissolution rates of various formulations, (2) reduce the number of cut-and-try
attempts to design new drug formulations, (3) design in vitro dissolution
experiments to better mimic in vivo (animal and human) conditions, and (4)
justify product specifications. Version 6.0 of DDDPlus was released in
· simulation of the in vitro dissolution of long-acting injectable dosage forms (funded by the FDA grant supporting GastroPlus development) · simulation of the in vitro dissolution of controlled release bead formulations · new simulation of artificial stomach-duodenum (ASD) experiments · ability to fit models from precipitation experiments · new dissolution apparatus models · improved output reporting MembranePlus™
Similar to DDDPlus, MembranePlus mechanistically simulates laboratory experiments, but in this case, the experiments are for measuring permeability or clearance of drug-like molecules through various membranes, including several different standard cell cultures (Caco-2, MDCK), as well as hepatocytes. The value of such simulations derives from the fact that when the same molecules are measured in different laboratories using (supposedly) the same experimental conditions, the results are often significantly different. These differences are caused by a complex interplay of factors in how the experiment was set up and run. MembranePlus simulates these experiments with their specific experimental details, and this enables scientists to better interpret how results from specific experimental protocols can be used to predict permeability or clearance mechanisms in human and animals.
26 PKPlus™
In
PKPlus version 2.5 was released in
· Import CDISC SEND packages with PC domain as source data · Improved command line functionality · 64-bit system optimization for improved performance · Streamlined auto-reports · Additional workflow refinements
Starting with version 2.0, we provide PKPlus for free to academics because we believe it will help educate the next generation of scientists entering the industries we serve and drive demand for the product. Hundreds of copies of PKPlus have been downloaded by universities around the world to date.
In
ADMET Predictor®
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ADMET Predictor has been top-ranked for predictive accuracy in multiple peer-reviewed, independent comparison studies for many years, while generating its results at a very high throughput rate. Although the state of the art of this type of software does not enable identifying the best molecule in a series, it does allow early screening of molecules that are highly likely to fail as potential drug candidates (i.e., the worst molecules, which is typically the majority of a virtual chemical library) before synthesizing and testing them. Thus, millions of virtual compounds can be created and screened in a day, compared to potentially months or years of work to actually synthesize and test a much smaller number of actual compounds.
The optional ADMET Modeler™ Module in ADMET Predictor enables scientists to use their own experimental data to quickly create proprietary high-quality predictive models using the same powerful artificial intelligence (AI) engine we use to build our top-ranked property predictions. Pharmaceutical companies expend substantial time and money conducting a wide variety of experiments on new molecules each year, generating large databases of experimental data. Using this proprietary data to build predictive models can provide a second return on their investment; however, model building has traditionally been a difficult and tedious activity performed by specialists. The automation in ADMET Modeler makes it easy for a scientist to create very powerful machine-learning/AI models with minimal training.
Version 9.5 was released in
· Novel approaches to calculate uncertainty estimates on all regression models · New machine learning models for important metabolism and transporter endpoints · New machine learning models forAMES mutagenicity, a primary toxicity endpoint required during risk assessment · New Structure Sensitivity Analysis visualization tool to easily map atom-level contributions to model predictions · Improved rat-specific models to more accurately inform HTPK Simulation predictions · Improved Pipeline Pilot and KNIME components to extend deployment options and enterprise support for ADMET Predictor · Updates to output displays in MedChem Designer™
We have made significant investments in two key areas with recent versions: improving integration of our top-ranked ADMET Predictor and GastroPlus models to leverage our novel 'Discovery PBPK' approaches for chemists and safety researchers, and further enhancing our best-in-class machine learning engine to assist with drug discovery. Recent publications from pharmaceutical and chemical companies describing how they have leveraged our 'Discovery PBPK' methods to guide lead optimization and risk assessment illustrate how our unique offerings provide substantial value in these spaces.
In
Potential new markets for artificial intelligence (machine learning)
We are currently investigating applications of our sophisticated artificial intelligence (machine-learning) engine.
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We believe our proprietary AI/machine learning software engine has a wide variety of potential applications and we intend to pursue funding to develop customized tools to further monetize our investment in this technology by expanding our markets beyond the life sciences and chemistry. In addition, we are examining a variety of expanded capabilities to add to the basic modeling engine to accommodate even larger data sets ("big data analytics") and new applications.
MedChem Designer™
MedChem Designer was initially a molecule-drawing program, or "sketcher", but
now has capabilities far exceeding those of other molecule-drawing programs
because of its integration with both
When used with a license for ADMET Predictor, MedChem Designer becomes a de novo molecule design tool. With it, a researcher can draw one or more molecular structures, then click on the ADMET Predictor icon and have approximately 150 properties for each structure calculated in seconds, including our proprietary ADMET Risk™ index which provides a single number that instantly compare the effects of different structural changes in many dimensions. Researchers can also click on an icon to generate the likely metabolites of a molecule and then predict all of the properties of those metabolites from ADMET Predictor, including each of their ADMET Risk scores. This is important because a metabolite of a molecule can be therapeutically beneficial (or harmful) even though the parent molecule is not.
MedChem Studio™
The MedChem Studio Module in ADMET Predictor is a powerful software tool that is
used both for data mining and for de novo design of new molecules. In its
data-mining role,
While MedChem Designer can be used to refine a small number of molecules, the
MedChem Studio Module can be used to create and screen very large numbers of
molecules down to a few promising lead candidates.
KIWI™
Drug development programs rely increasingly on modeling and simulation analyses to support decision-making and submissions to regulatory agencies. To ensure high-quality reproducible analyses, organizations must not only apply high-quality scientific methods, but must also be able to support the science with validated results. KIWI is a cloud-based web application that was developed to efficiently organize, process, maintain, and communicate data and results generated by pharmacometricians and scientists over the duration of a drug development program. The validated workflow and tools within KIWI promote traceability and reproducibility of results.
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The pharmaceutical industry has been rapidly adopting cloud technology as a solution to ever-expanding computer processing needs. Leveraging our 20-plus years of experience in providing an architecture supporting modeling and simulation efforts, we have developed KIWI as a secure, validated, enterprise-scale environment, enabling global teams to collaborate on model-based decision making. KIWI has proven to be a valuable platform for encouraging interdisciplinary discussions about the model development process and interpretation of results. We regularly receive positive feedback about the functionality implemented in KIWI and the value of the approach we have taken to harness cloud technology. We continue to improve functionality and collaboration within the KIWI platform, and we expect the licensing fee will be a source of recurring revenue for further development and growth.
We release new versions of the program on a regular basis. KIWI Version 2 was
released in
KIWI 4 was released in
We continue enhancing KIWI as part of our five-year, almost-$5 million contract
with the
DILIsym
The DILIsym software is a quantitative systems pharmacology (QSP) program that has been in development since 2011. QSP software models are based on the fundamental understanding of complex biological pathways, disease processes, and drug mechanisms of action, integrating information from experiments and forming hypotheses for the next experimental model. DILIsym deals with the propensity for some drug molecules to induce temporary or permanent changes in biological functions within liver cells (hepatocytes) that can result in damage to the liver. Some drugs cause temporary changes in liver function but the body soon compensates and liver function returns to normal. Other drugs cause liver function to permanently decline as they continue to be taken. The DILIsym software models a variety of interactions within the hepatocytes to determine whether a particular drug molecule interrupts normal signaling pathways in a manner to induce injury to the cells.
Version 8A of the DILIsym software was released in January of 2019. This version is again delivered as a secure executable that incorporates new proprietary code enabling tighter integration with our GastroPlus PBPK software. Securing the code is necessary to ensure that results are consistent across all users to assure regulatory agencies that the calculated results are from a validated version. Open source programs are subject to modification by the user and so each use could have a different set of calculations, so validation would not be assured. In addition, a number of important new capabilities were added:
· 10 New validation compounds · New Cholestatic liver injury mechanism · New Oxidative stress (ROS) NRF2 adaptation response framework · New Human SimPops with variability in bilirubin processing pathways · New Liver injury biomarker GLDH · Live DILIsym documentation website updated with new training resources 30 NAFLDsym
Where DILIsym is used to investigate the likelihood that a known drug molecule
would cause injury to the liver, NAFLDsym is concerned with a liver that is
already diseased (NAFLD/
RENAsym
Where DILIsym is used to investigate the likelihood that a known drug molecule
would cause injury to the liver, RENAsym will be focused on investigating and
predicting drug-induced kidney injury, or acute kidney injury (AKI). RENAsym
will be another "shrink wrap" software product, usable across many companies and
drug development projects. The software will utilize predictions of drug
exposure in the kidney from PBPK platforms such as GastroPlus, along with in
vitro data related to certain kidney injury mechanisms, to make predictions. The
first expected release of RENAsym will be available towards the end of 2020. The
initial development is being funded via an
IPFsym
IPFsym is a software tool that will investigate the likelihood that various molecules might provide beneficial therapeutic benefits to treat or cure idiopathic pulmonary fibrosis (IPF). IPFsym, like NAFLDsym, requires modification for each of a number of different mechanisms of action that potential new drug compounds could use to treat the disease, and so is a customized tool used in consulting projects for each new client project. IPFsym is targeted for release for licensing and consulting use sometime in 2021. The software will include the most important mechanisms of IPF and will be closely coupled with GastroPlus for drug concentration predictions within the lungs.
In
Our scientists and engineers have expertise in drug absorption via various dosing routes (oral, intravenous, subcutaneous, intramuscular, ocular, nasal/pulmonary, and dermal), pharmacokinetics, pharmacodynamics, and drug-drug interactions. They have attended over 200 scientific meetings worldwide in the past four years, often speaking and presenting. We conduct contracted consulting studies for large customers (including many of the top twenty pharmaceutical companies) who have particularly difficult problems and who recognize our expertise in solving them, as well as for smaller customers who prefer to have studies run by our scientists rather than to license our software and train someone to use it. The demand for our consulting services has been steadily increasing, and we have expanded our consulting teams to meet the increased workload.
Currently we are entering year four of a five-year consulting agreement with the
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We have a reputation for high-quality analyses and regulatory reporting of data
collected during preclinical experiments as well as clinical trials of new and
existing pharmaceutical products, typically working on 80-100 drug projects per
year. Traditionally, the model-based analysis of clinical trial data was
different from the modeling analysis offered by GastroPlus or our quantitative
systems toxicology/pharmacology software (DILIsym and NAFLDsym); the former
relied more on statistical and semi-mechanistic models, whereas the latter is
based on very detailed mechanistic models. Statistical models rely on direct
observation and mathematical equations that are used to fit data collected
across multiple studies along with describing the variability within and between
patients. Mechanistic models are based on a detailed understanding of the human
body and the chemistry of the drug and involve deep mathematical and scientific
representation of the phenomena involved in drug dissolution/precipitation,
absorption, distribution, metabolism, and elimination. Collectively, the models
support safety and efficacy decisions, first-in-human estimations, formulation
optimization, and drug-drug interaction assessments. Beginning in 2014, the
PRODUCT DEVELOPMENT
Development of our software is focused on expanding product lines, designing enhancements to our core technologies, and integrating existing and new products into our principal software architecture and platform technologies. We intend to continue to offer regular updates to our products and to continue to look for opportunities to expand our existing suite of products and services.
To date, we have developed products internally, sometimes also licensing or acquiring products, or portions of products, from third parties. These arrangements sometimes require that we pay royalties to third parties. We intend to continue to license or otherwise acquire technology or products from third parties when it makes business sense to do so. We currently have one license agreement, pursuant to which a small royalty is paid based on revenues on each license for the Metabolism Module in ADMET Predictor.
In 1997 we entered into an exclusive software licensing agreement with
MARKETING AND DISTRIBUTION
We distribute our products and offer our services in
We market our pharmaceutical software and consulting services through attendance and presentations at scientific meetings, exhibits at trade shows, seminars at pharmaceutical companies and government agencies, through our website, and using various communication channels to our database of prospects and customers. At various scientific meetings around the world each year there are numerous presentations and posters presented in which the reported research was performed using our software. Many of these presentations are from industry and FDA scientists; some are from our staff. In addition, more than 100 peer-reviewed scientific journal articles, posters, and podium presentations are typically published each year using our software, mostly by our customers, further supporting its use in a wide range of preclinical and clinical studies.
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Our sales and marketing efforts are handled primarily internally by sales and
marketing staff and with our scientific team and several senior management staff
assisting our marketing and sales staff with trade shows, seminars, and customer
trainings both online and on-site. We also have independent distributors in
We provide support to the
PRODUCTION
Our pharmaceutical software products are designed and developed by our
development teams in
COMPETITION
In our pharmaceutical software and services business, we compete against a
number of established companies that provide screening, testing and research
services, and products that are not based on simulation software. There are also
software companies whose products do not compete directly with, but are
sometimes closely related to, ours. Our competitors in this field include some
companies with financial, personnel, research, and marketing resources that are
larger than ours. Our flagship product, GastroPlus, is the most widely used
commercial PBPK modeling platform and has one significant competitor; others
could be developed over time, but with the high barrier to entry, it would be
difficult to validate new software to levels required to support regulatory
submissions. Our PKPlus software product competes with one major and a few minor
software programs.
Major pharmaceutical companies conduct drug discovery and development efforts through their internal development staffs and through outsourcing. Smaller companies generally need to outsource a greater percentage of this research. Thus, we compete not only with other software suppliers and scientific consulting service providers, but also with the in-house development and scientific consulting teams at some of the larger pharmaceutical companies.
Although competitive products exist, both new licenses and license renewals for
GastroPlus have continued to grow. We believe that we enjoy a dominant market
share in this segment. We believe our ADMET Predictor/ADMET Modeler,
Based on our technical knowledge and expertise, the Company is strategically placed to offer modeling and simulation consulting services to companies. Our clients seek out our services for multiple reasons: (1) to acquire scientific, therapeutic area related or modeling expertise that they do not have in-house, (2) to address an excess of modeling and simulation requirements beyond the capacity of in-house resources, (3) to fulfill their modeling requirements more efficiently than they could do in-house, and (4) to utilize our software when they do not have the in-house expertise to do so. We apply our software and assist companies in such areas as: physiologically based pharmacokinetic modeling (PBPK), pharmacokinetic/pharmacodynamic (PK/PD) data analysis; and quantitative systems pharmacology/toxicology (QSP/T). We compete against numerous service providers, ranging from departments within large contract research organizations (CROs) to independent consulting organizations of various sizes as well as individual consultants.
We believe the key factors in our ability to successfully compete in this field are our ability to: (1) continue to invest in research and development, and develop and support industry-leading simulation and modeling software and related products and services,(2) develop and maintain a proprietary database of results of physical experiments that serve as a basis for simulated studies and empirical models, (3) continue to attract and retain a highly skilled scientific and engineering team, (4) aggressively promote our products and services to our global market, and (5) develop and maintain relationships with research and development departments of pharmaceutical companies, universities, and government agencies
In addition, we actively seek strategic acquisitions to expand both our pharmaceutical software and services business.
33 Results of Operations
Comparison of Three Months Ended
The following table sets forth our condensed statements of operations (in thousands) and the percentages that such items bear to net sales (because of rounding, numbers may not foot):
Three Months Ended 11/30/19 11/30/18 Net revenues$ 9,401 100.0%$ 7,536 100.0% Cost of revenues 2,643 28.1 2,200 29.2 Gross profit 6,758 71.9 5,336 70.8
Selling, general and administrative 3,513 37.4 2,719 36.1 Research and development
526 5.6 530 7.0 Total operating expenses 4,040 43.0 3,249 43.1 Income from operations 2,719 28.9 2,087 27.7 Other income 15 0.2 (65 ) (0.9 )
Income from operations before taxes 2,734 29.1 2,020 27.0 (Provision for) income taxes
(675 ) (7.2 ) (486 ) (6.4 ) Net income$ 2,058 21.9%$ 1,536 20.4% Net Revenues
Consolidated net revenues increased by 24.8% or
·
·
$2.39 million
·
to$2.09 million
Consolidated software and software-related sales increased
Cost of Revenues
Consolidated cost of revenues increased by
Cost of Revenues as a percentage of revenue decreased by 1.1% in 1QFY20 to 28.1% as compared to 29.2% in 1QFY19.
34 Gross Profit
Consolidated gross margin increased
Overall gross margin percentage increased by 0.9% to 71.9% in 1QFY20 from 70.8% in 1QFY19.
Selling, General and Administrative Expenses
Selling, general, and administrative (SG&A) expenses increased
The major increases in SG&A expense were:
· G&A Salaries and Wages increased by
of increased stock compensation costs, increased costs associated with the
new CEO, annual salary increases and increased head count in
personnel.
· Commission expense:
· Director fees:
· Insurance Expense
cost increases and higher employee counts and
related insurance.
· Payroll tax expense increased
· Professional Fees:
legal costs
· Software licenses:
Research and Development
Total research and development costs increased by
Other income (expense)
Other income was
Provision for Income Taxes
The provision for income taxes was
Net Income
Net income increased by
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Liquidity and Capital Resources
Our principal sources of capital have been cash flows from our operations. We have achieved continuous positive operating cash flow over the last ten fiscal years. We believe that our existing capital and anticipated funds from operations will be sufficient to meet our anticipated cash needs for working capital and capital expenditures for the foreseeable future. Thereafter, if cash generated from operations is insufficient to satisfy our capital requirements, we may open a revolving line of credit with a bank, or we may have to sell additional equity or debt securities or obtain expanded credit facilities. In the event such financing is needed in the future, there can be no assurance that such financing will be available to us, or, if available, that it will be in amounts and on terms acceptable to us. If cash flows from operations became insufficient to continue operations at the current level, and if no additional financing was obtained, then management would restructure the Company in a way to preserve its pharmaceutical business while maintaining expenses within operating cash flows.
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