Item 1. Business
Item
1. Business
Overview
We
are a diversified life sciences company focused on developing treatments for adult and pediatric cancers with potential for Orphan Drug
designation, while also commercializing diagnostics.
Our
cancer therapeutics pipeline includes QN-302, RAS (formerly RAS-F) and QN-247.
Our
lead oncology therapeutics program, QN-302, is an investigational small molecule G-quadruplexes (G4)-selective transcription
inhibitor with strong binding affinity to G4s prevalent in cancer cells. Such binding could, by stabilizing the G4s against DNA
“unwinding,” help inhibit cancer cell proliferation. QN-302 is currently undergoing Good Laboratory Practice (GLP) toxicology
studies.
Our
RAS portfolio consists of a family of RAS oncogene protein-protein interaction inhibitor small molecules believed to inhibit or block
mutated RAS genes’ proteins from binding to their effector proteins. Preventing this binding could stop tumor growth, especially
in RAS-driven tumors such as pancreatic, colorectal and lung cancers.
Our
investigational QN-247 compound binds nucleolin, a key multi-functional regulatory phosphoprotein that is overexpressed in cancer cells.
Such binding could inhibit the cancer cells’ proliferation. The foundational aptamer of QN-247 is QN-165 (formerly referred to
as AS1411), which the Company has deprioritized as a drug candidate for treating COVID-19 and other viral-based infectious diseases.
In
addition to our oncology drug pipeline, we have an established diagnostics business.
Our
revenue driver is our FastPack proprietary blood-based diagnostics platform which includes diagnostic instruments and test kits that
are sold commercially primarily in the United States, as well as certain European countries. The FastPack System menu includes a rapid,
highly accurate immunoassay diagnostic testing system for cancer, men’s health, hormone function, and vitamin D status. We provide
analyzers to our customers (physician offices, clinics and small hospitals) at low cost in order to increase sales volumes of higher-margin
test kits.
On
May 26, 2022, we acquired a 52.8% interest in NanoSynex, Ltd. (“NanoSynex”). NanoSynex is a micro-biologics diagnostic company
domiciled in Israel. NanoSynex’s technology is an Antimicrobial Susceptibility Testing (AST) that aims to enable better targeting
of antibiotics for their most suitable uses to ultimately result in faster and more efficacious treatment, hence reducing hospitals mortality
and morbidity rates. See Part II, Item 7 “ Management’s Discussion and Analysis of Financial Condition and Results of Operations ”
for additional details.
Completion
of Reverse Recapitalization Transaction with Ritter Pharmaceuticals, Inc.
On
May 22, 2020, we completed a “reverse recapitalization” transaction with Qualigen, Inc. (not to be confused with the Company);
pursuant to which our merger subsidiary merged with and into Qualigen, Inc. with Qualigen, Inc. surviving as a wholly owned subsidiary
of the Company. The Company, which had previously been known as Ritter Pharmaceuticals, Inc., was renamed Qualigen Therapeutics, Inc.,
and the former stockholders of Qualigen, Inc. acquired, via the recapitalization, a substantial majority of the shares of the Company.
Ritter/Qualigen Therapeutics common stock, which was previously traded on the Nasdaq Capital Market under the ticker symbol “RTTR,”
commenced trading on Nasdaq, on a post-reverse-stock-split adjusted basis, under the ticker symbol “QLGN” on May 26, 2020.
We are no longer pursuing the gastrointestinal disease treatment business on which Ritter Pharmaceuticals, Inc. had focused before the
reverse recapitalization transaction.
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Cancer
Drug Pipeline and Diagnostic Products
Therapeutics
Pipeline
Our
lead drug compound QN-302 (formerly SOP1812) is being developed to target regulatory regions of cancer genes that down-regulate gene
expression in multiple cancer pathways for potential treatment of G4-targeted tumors ( e.g. , pancreatic cancer). The investigational
compounds within our RAS portfolio are designed to suppress the interaction of endogenous RAS with c-RAF, upstream of the KRAS, HRAS
and NRAS effector pathways. Our anticancer drug candidate, QN-247 (formerly referred to as ALAN or AS1411-GNP) is aptamer-based and currently
in development to treat a variety of cancer types, including liquid and solid tumors.
Our
deprioritized programs (and thus not featured in the chart above) include QN-165 (formerly referred to as AS1411), a drug candidate for
the potential broad-spectrum treatment of infectious diseases such as COVID-19, and our Selective Target Antigen Removal System (STARS),
a therapeutic device product concept, currently in discovery stage, designed to remove circulating tumor cells, viruses, inflammation
factors and immune checkpoints.
QN-302
(formerly referred to as SOP1812)
We
exclusively in-licensed the global rights to the G4 selective transcription inhibitor platform from University College London
(“UCL”) in January 2022. The licensed technology comprises lead compound QN-302 (formerly SOP1812) and back-up compounds
that target regulatory regions of cancer genes that down-regulate gene expression in multiple cancer pathways. Developed by Dr.
Stephen Neidle and his group at UCL, the G-Quadruplex (G4) binding concept is derived from over 30 years in nucleic acid research,
including research on G4s, which are higher order DNA and RNA structures formed by sequences containing guanine-rich repeats. G4s
are overrepresented in telomeres (a region of repetitive DNA sequences at the end of a chromosome) as well as promoter sequences and
untranslated regions of many oncogenes. Their prevalence is therefore significantly greater in cancer cells compared to normal human
cells.
G4-selective
small molecules such as QN-302 and backup compounds target the regulatory regions of cancer genes, which have a high prevalence of enriched
G4s. Stable G4-QN-302 complexes can be impediments to replication, transcription or translation of those cancer genes containing G4s,
and the drugs’ binding to G4s are believed to stabilize the G4s against possible “unwinding.” G4 binders like QN-302
could be efficacious in a variety of cancer types with a high prevalence of G4s.
Pancreatic
cancer is the tenth most common cancer and third deadliest cancer in the United States and has one of the lowest rates of survival of
all cancer types, with 91% of those diagnosed dying from the disease and one in four dying within the first month of diagnosis. The chemotherapy
drug Gemcitabine has been standard of care for patients with metastatic pancreatic cancer for more than 15 years. Numerous clinical trials
have tested new drugs, either alone or in combination, with Gemcitabine. We believe that QN-302 has the potential to demonstrate superior
efficacy and activity against pancreatic ductal adenocarcinoma (“PDAC”) compared to existing agents, with a distinct mechanism
of action and promising preclinical target profile.
In-vitro
and in-vivo studies have shown that G4 stabilization by QN-302 resulted in inhibition of target gene expression and cessation
of cell growth in various cancers, including PDAC, which represents 98% of pancreatic cancers. In in-vitro studies, QN-302 was
potent in inhibiting the growth of several PDAC cell lines at low nanomolar concentrations. Similarly, in in-vivo studies, QN-302
showed a longer survival duration in a KPC genetic mouse model for pancreatic cancer than Gemcitabine has historically shown. Additional
preclinical in-vivo studies suggest activity in gemcitabine-resistant PDAC. Data further demonstrated that QN-302 had significant
anti-tumor activity in three patient-derived PDAC xenograft models. Early safety indicators suggest no significant adverse toxic effects at
proposed therapeutic doses in pancreatic cancer mouse in-vivo models.
On
January 9, 2023, the U.S. Food and Drug Administration (“FDA”) granted Orphan Drug Designation (“ODD”) to QN-302
for the indication of pancreatic cancer. ODD provides advantages to pharmaceutical companies that are developing investigational drugs
or biological products that show promise in treating rare diseases or conditions that affect fewer than 200,000 people in the United
States, including seven-year marketing exclusivity and eligibility to receive regulatory support and guidance from the FDA in the design
of an overall drug development plan.
5
There
are also economic advantages to receiving ODD, including a 25% federal tax credit for expenses incurred in conducting clinical research
on the orphan designated product within the United States. Tax credits may be applied to the prior year or applied to up to 20 years
of future taxes. ODD recipients may also have their Prescription Drug User Fee Act (PDUFA) application fees waived, a potential savings
of around $3.2 million (as of fiscal year 2023) for applications requiring covered clinical data, and may qualify to compete for research
grants from the Office of Orphan Products Development that support clinical studies.
RAS
(formerly RAS-F)
In
July 2020, we entered into an exclusive worldwide license agreement with University of Louisville (“UofL”) for the intellectual
property covering the “RAS” family of pan RAS inhibitor small molecule drug candidates,
which are believed to work by blocking RAS mutations directly, thereby inhibiting tumor formation (especially in pancreatic, colorectal
and lung cancers). Pursuant to the license agreement, we in-licensed the “RAS” compound family of drug candidates and will
seek to identify and develop a lead drug candidate from the compound family and, upon commercialization, will pay UofL royalties in the
low-to-mid-single-digit percentages on net sales of RAS inhibitor licensed products.
RAS
is the most common oncogene in human cancer. Activating mutations in one of the three human RAS gene isoforms (KRAS, HRAS or NRAS) are
present in about one-fourth to one-third of all cancers. For example, mutant KRAS is found in 98% of pancreatic ductal adenocarcinomas,
52% of colon cancers, and 32% of lung adenocarcinomas. For these three cancer types, cancers with mutant KRAS are diagnosed in more than
170,000 people each year in the United States and cause more than 120,000 deaths. Drugs that target signaling downstream of RAS are available; however, such drugs have shown disappointing clinical
durability because RAS is a “hub” that activates multiple effectors, so drugs that block a single pathway downstream may
not account for the many other activated pathways.
In
March 2022 and October 2022, we signed amendments to our sponsored research agreement with UofL to extend our partnership. Under the
amended agreement, the collaboration extends until the third quarter of 2023 and commits additional resources to support ongoing discovery
and preclinical efforts for the RAS platform.
QN-247
(formerly referred to as ALAN or AS1411-GNP)
QN-247
is an oligonucleotide-based drug candidate that is designed to treat different types of nucleolin-expressing cancers, including liquid and solid tumors. QN-247
inhibits nucleolin, a key multi-functional regulatory phosphoprotein that is overexpressed in cancer cells, and may thereby be able to inhibit
the cells’ proliferation. QN-247 has shown promise in preclinical studies for the treatment of acute myeloid leukemia (“AML”).
This novel technology may have several other potential applications, including enhancement of radiation therapy, enhancement of tumor
imaging, and delivery of other anti-cancer compounds directly to tumor cells.
QN-247 is an enhanced version of QN-165 (which in turn was formerly referred
to as AS1411), where the DNA oligonucleotide aptamer is conjugated. A key component of QN-247, DNA oligonucleotide aptamer QN-165, has
been shown, primarily on a preclinical basis, to have the potential to target and destroy cancer cells. This component has been administered
in Phase 1 and Phase 2 clinical trials to over 100 AML or renal cell carcinoma cancer patients and appears to be well tolerated with no
evidence of severe adverse events in such trials, with at least seven patients appearing to have clinical responses.
An in vivo efficacy study with
a triple negative breast cancer (TNBC) MDA-MB-231 xenograft mouse model was performed with 12 daily doses (1 mg/kg) of QN-247. This study
showed statistically significant reductions in mean tumor volumes for all QN-247 formulations compared to baseline and to vehicle control.
QN-247 formulations with higher oligonucleotide loading appeared to reduce tumor volumes more than lower oligonucleotide loading. No evidence
of adverse toxicity was observed.
We
entered into a sponsored research agreement with UofL in August 2018 which was subsequently amended in October 2020, pursuant to which
UofL performed various animal studies to assess antitumor efficacy and safety of different QN-247 compositions. The sponsored research
agreement with UofL for QN-247 expired on August 31, 2022, and the license agreement with UofL for QN-247 was amended on January 9, 2023.
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QN-165
(formerly referred to as AS1411)
In
June 2020, we entered into an exclusive royalty-bearing license agreement with UofL for UofL’s intellectual property for the use
of QN-165 as a drug candidate for the treatment of COVID-19. In September 2020 we and UofL jointly filed a U.S. provisional patent application,
entitled “Methods of inhibiting or treating coronavirus infection, and methods for delivering an anti-nucleolin agent.” The
application was filed in conjunction with Drs. Paula J. Bates and Kenneth E. Palmer from UofL, and covers methods for using QN-165 as
an antiviral drug candidate to prevent SARS-CoV-2 from entering the body through mucous membranes in the nose, mouth and eyes. As stated
in the patent application, we believe that QN-165 could be administered by means of inhalers, nose spray or eye drops to individuals
who have recently come in contact with SARS-CoV-2, or are at high risk of contracting the virus.
We
believe that the mechanism by which QN-165 is believed to work, by blocking the ability of viruses to replicate in the body, may also
make the drug candidate effective against future mutations in COVID-19 as well as against other dangerous viruses including seasonal
influenza. Moreover, we believe that in addition to its proposed use as a therapeutic, QN-165 might be able to be used as a protective
defense or prophylaxis against COVID-19 and/or other viral-based diseases such as seasonal influenza.
On
July 13, 2021, we submitted an Investigational New Drug (“IND”) application with the FDA seeking approval to commence Phase
1b/2a clinical studies of QN-165 in hospitalized COVID-19 patients. On August 11, 2021, the FDA informed us that additional preclinical
studies would be required for the IND application to be cleared to proceed into the clinic with QN-165. We then decided to allocate our
resources to focus on our oncology pipeline, and deprioritized the development of QN-165 program. Qualigen is seeking to out-license
QN-165 to a partner that has interest and expertise in antiviral development, such as dengue, influenza, RSV and other infectious diseases.
Due to its mechanism and in vivo potency, we believe that QN-165 could potentially be developed as a first-line treatment against emerging
viruses and biothreats.
FastPack ®
The
FastPack System is a patent-protected rapid, onsite immunoassay testing system consisting of the FastPack Analyzer and the FastPack test
pouch, a single-use, disposable, foil packet which includes the FastPack reagent chemistry. Since the initial conception of the system,
we have developed successive versions of the analyzer and test pouch, known as “1.0,” “IP” and “PRO”,
and have expanded our assay menu to nine tests, including tests for prostate cancer, thyroid function, metabolic disorders, and research
applications. We have sold FastPack products in the United States and overseas for over 20 years, and since inception, our sales of FastPack
products have exceeded $127 million. We manufacture the FastPack products at our FDA and International Standards Organization (“ISO”)
certified Carlsbad, California facility. As of April 2022 most FastPack sales are distributed through various distribution partners in
North America as well as in Europe (primarily Axon Labs in Germany and Switzerland). We also sell direct to clinics and physician offices
located throughout North America.
In
July 2020, we submitted an official notification to the FDA to commence sales in the United States of our FastPack SARS-CoV-2 IgG test
for COVID-19 antibodies, which was designed for use with our new FastPack PRO. The test was previously submitted to the FDA for Emergency
Use Authorization (“EUA”). In April 2021, we withdrew this EUA. During the nine months during which the EUA was with the
FDA, alternative tests and testing practices became widespread and we determined that there was no longer a viable business case for
scale-up of the test.
Strategic
Partners
In
January 2022, we entered into a royalty-bearing license agreement with UCL, with respect to intellectual property and know-how covering
lead and backup compounds for our G4 selective transcription inhibitor program, QN-302.
We
are party to a royalty-bearing license agreement with UofL for the development of RAS and the QN-247 program.
We
in-license patents from DIAsource ImmunoAssays S.A. and Future Diagnostics B.V., for reagents that are used in our FastPack Vitamin D
assay.
Sales
Channels
Prior
to April 2022, most of our FastPack sales were through our diagnostics distribution partner Sekisui Diagnostics, LLC (“Sekisui”)
pursuant to a distribution agreement. The distribution agreement with Sekisui expired on March 31, 2022, at which time the activities
formerly provided by Sekisui reverted to us. As of April 2022, most of our FastPack sales are through various distribution partners in
North America, including McKesson Medical-Surgical, Henry Schein Medical, Medline Industries and National Distribution & Contracting,
the largest distributors of physician office laboratory products in the United States. Outside of the United States, we sell the FastPack
product line through a network of distributors in Europe (primarily Axon Labs in Germany and Switzerland). We also continue to sell our
testosterone test kits directly to Low T Center, Inc. (“Low T”), the largest men’s health group in the United States,
with 40 locations. Low T was acquired by SynergenX in September 2022. The combined company currently operates 64 locations.
7
Product
sales to McKesson accounted for 48% of our total revenues and product sales to Low T accounted for 26% of our total revenues during the
fiscal year ended December 31, 2022. The remaining revenue was comprised of product sales and warranties to other distributors and direct
sales accounts.
In
October 2020, we entered into an agreement with Yi Xin Zhen Duan Jishu (Suzhou) Ltd (“Yi Xin”), pursuant to which we granted
Yi Xin exclusive rights to manufacture and sell new generations of FastPack-based products as well as Yi Xin-manufactured versions of
our existing FastPack 1.0, IP and PRO product lines in China. We are entitled to receive royalties on any such sales. After May 1, 2022,
Yi Xin has the right to sell its new generations of FastPack-based diagnostic test systems throughout the world, other than to our then-current
FastPack customers; and on a worldwide basis, except in the United States, Yi Xin also has the right to sell Yi Xin-manufactured versions
of our existing FastPack 1.0, IP and PRO product lines. We are entitled to receive royalties on any of these sales. After March 31, 2022,
Yi Xin has the right to buy Qualigen FastPack 1.0, IP and PRO products from us at distributor prices for resale in the United States,
again excluding resales toward our then-current FastPack customers.
Manufacturing
We
develop, manufacture and assemble our diagnostic products at our approximately 23,000 square feet facility in Carlsbad, California. Our
laboratory and manufacturing practices are governed by a series of internally published Standard Operating Procedures, in accordance
with FDA and ISO guidelines. While we produce many of our own raw materials and sub-components for diagnostic products, we also purchase
certain materials from third-party suppliers such as Amcor, Enstrom, Gilson, Hi-Tech Products, Hamamatsu, Sigma Aldrich, Surmodics, 3M,
Thermo Fisher Scientific, and VWR International.
We
do not have in-house manufacturing capability for our therapeutics product candidates.
Research
and Development
For
research and development of our drug candidates, we are leveraging the scientific and technical resources and laboratory facilities of
UofL and UCL, through technology licensing, sponsored research, and other consulting agreements, which are focused on aptamer technology
and applications. We would engage contract research organizations (“CROs”) for any clinical trials of our drug candidates.
We intend to focus our internal research and development on oversight of these organizations and continuing support of the FastPack diagnostic
line.
Regulatory
Matters
We
have obtained 17 FDA clearances/approvals and 28 CE Marks for our diagnostic products (FastPack analyzers, immunoassays, control kits,
calibration kits and verifications kits) to date. We have not obtained FDA or other regulatory approval for any drug candidate.
Medical
Device Regulatory Clearances and Approvals
The
medical devices that we manufacture and market are subject to regulation by numerous worldwide regulatory bodies, including the FDA and
comparable international regulatory agencies. These agencies require manufacturers of medical devices to comply with applicable laws
and regulations governing development, testing, manufacturing, labeling, marketing and distribution. Medical devices are also generally
subject to varying levels of regulatory control based on the risk level of the device.
In
the United States, unless an exemption applies, before we can commercially distribute medical devices, we must obtain, depending on the
type of device, either premarket notification clearance or premarket approval (“PMA”) from the FDA. The FDA classifies medical
devices into one of three classes. Devices deemed to pose lower risks are placed in either class I or II, which typically requires the
manufacturer to submit to the FDA a premarket notification requesting permission to commercially distribute the device. Some low-risk
devices are exempted from this requirement. Devices deemed by the FDA to pose the greatest risks, such as life-sustaining, life-supporting
or implantable devices, or devices deemed not substantially equivalent to a previously cleared device, are placed in class III, generally
requiring PMA.
The
premarket notification process requires that a premarket notification (510(k)) be made to the FDA to demonstrate that a new device is
as safe and effective as, or substantially equivalent to, a legally marketed device (the “predicate” device). This process
is generally known as obtaining 510(k) clearance for a new device. Under this process, applicants must submit performance data to establish
substantial equivalence. In some instances, data from human clinical trials must also be submitted in support of a 510(k) premarket notification.
If so, these data must be collected in a manner that conforms to the applicable Investigational Device Exemption (“IDE”)
regulations. The FDA must issue a decision finding substantial equivalence before commercial distribution can occur. Changes to cleared
devices that do not significantly affect the safety or effectiveness of the device can generally be made without additional 510(k) premarket
notifications; otherwise, a new 510(k) is required.
8
The
PMA approval process requires the submission of a PMA application to the FDA to demonstrate that the new device is safe and effective
for its intended use. This approval process applies to most Class III devices and generally requires clinical data to support the safety
and effectiveness of the device, obtained in adherence with IDE requirements. The FDA will approve the PMA application if it finds that
there is a reasonable assurance that the device is safe and effective for its intended purpose and that the proposed manufacturing is
in compliance with the Quality System Regulation (“QSR”). For novel technologies, the FDA may seek input from an advisory
panel of medical experts and seek their views on the safety, effectiveness and benefit-risk of the device. The PMA process is generally
more detailed, lengthier and more expensive than the 510(k) process.
In
the European Union (“EU”), we are required to comply with the In-Vitro Diagnostic Regulation (“IVDR”), which
became effective May 2021, superseding existing Medical Device Directives. Medical devices that have a valid EC Certificate to the prior
Directives (issued before May 2021) can continue to be sold until May 2025 or until the EC Certificate expires, whichever comes first,
providing there are no significant changes to the design or intended use. The CE Mark, which is required to sell medical devices in the
EU is affixed following a Conformity Assessment and either approval from the appointed independent Notified Body or through self-certification
by the manufacturer. The selected pathway to CE marking is based on device risk classification. CE marking indicates conformity to the
applicable General Safety and Performance Requirements (“GSPRs”) for the IVDR. The IVDR changes multiple aspects of the regulatory
framework for CE marking, such as increased clinical evidence requirements, changes to labeling, and new requirements, including Unique
Device Identification (“UDI”), and many new post-market reporting obligations. IVDR also modifies and increases the compliance
requirements for the medical device industry and will continue to require significant investment to transition all products by May 2025.
The CE mark continues to be a prerequisite for successful registration in many other global geographies.
We
are also required to comply with the regulations of every other country where we commercialize products before we can launch or maintain
new products on the market.
The
FDA and other worldwide regulatory agencies and competent authorities actively monitor compliance to local laws and regulations through
review and inspection of design and manufacturing practices, record-keeping, reporting of adverse events, labeling and promotional practices.
The FDA can ban certain medical devices, detain or seize adulterated or misbranded medical devices, order recall or market withdrawal
of these devices and require notification of health professionals and others with regard to medical devices that present unreasonable
risks of substantial harm to the public health. The FDA may also enjoin and restrain a company for certain violations of the Food, Drug
and Cosmetic Act (“FDCA”) and the Safe Medical Devices Act, pertaining to medical devices, or initiate action for criminal
prosecution of such violations. Regulatory agencies and authorities in the countries where we do business can halt production in or distribution
within their respective country or otherwise take action in accordance with local laws and regulations.
International
sales of medical devices manufactured in the United States that are not approved by the FDA for use in the United States, or that are
banned or deviate from lawful performance standards, are subject to FDA export requirements. Additionally, exported devices are subject
to the regulatory requirements of each country to which the device is exported. Some countries do not have medical device regulations,
but in most foreign countries, medical devices are regulated. Frequently, regulatory approval may first be obtained in a foreign country
prior to application in the United States due to differing regulatory requirements; however, other countries, require approval in the
country of origin first. Most countries outside of the United States require that product approvals be recertified on a regular basis.
The recertification process requires the evaluation of any device changes and any new regulations or standards relevant to the device
and, where needed, conduct appropriate testing to document continued compliance. Where recertification applications are required, they
must be approved in order to continue selling our products in those countries.
Medical
Device Quality Assurance
We
are committed to providing high quality products to our customers and the patients they serve. Our quality system starts with the initial
product specification and continues through the design of the product, component specification process and the manufacturing, sale and
servicing of the product. Our quality system is intended to build in quality and process control and to utilize continuous improvement
concepts throughout the product life. Our quality system is also designed to enable us to satisfy various international quality system
regulations, including those of the FDA with respect to products sold in the United States. All of our medical device manufacturing facilities
and distribution centers are certified under the ISO 13485 quality system standard, established by the ISO for medical devices, which
includes requirements for an implemented quality system that applies to component quality, supplier control, product design and manufacturing
operations. This certification can be obtained only after a complete audit of a company’s quality system by an independent outside
auditor, and maintenance of the certification requires that these facilities undergo periodic re-examination.
United
States—FDA Drug Approval Process
The
research, development, testing, and manufacture of product candidates are extensively regulated by governmental authorities in the United
States and other countries. In the United States, the FDA regulates drugs under the FDCA and its implementing regulations.
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The
steps required to be completed before a drug may be marketed in the United States include, among others:
● preclinical
laboratory tests, animal studies, and formulation studies, all performed in accordance with
the FDA’s Good Laboratory Practice (“GLP”) regulations;
● submission
to the FDA of an IND application for human clinical testing, which must become effective
before human clinical trials may begin and for which progress reports must be submitted annually
to the FDA;
● approval
by an independent institutional review board (“IRB”) or Ethics Committee (“EC”)
at each clinical trial site before each trial may be initiated;
● adequate
and well-controlled human clinical trials, conducted in accordance with applicable IND regulations,
Good Clinical Practices (“GCP”), and other clinical trial related regulations,
to establish the safety and efficacy of the drug for each proposed indication to the FDA’s
satisfaction;
● submission
to the FDA of a New Drug Application (“NDA”) and payment of user fees for FDA
review of the NDA (unless a fee waiver applies);
● satisfactory
completion of an FDA pre-approval inspection of one or more clinical trial site(s) at which
the drug was studied in a clinical trial(s) and/or of us as a clinical trial sponsor to assess
compliance with GCP regulations;
● satisfactory
completion of an FDA pre-approval inspection of the manufacturing facility or facilities
at which the drug is produced to assess compliance with current GMPs regulations;
● agreement
with the FDA on the final labeling for the product and the design and implementation of any
required Risk Evaluation and Mitigation Strategy (“REMS”); and
● FDA
review and approval of the NDA, including satisfactory completion of an FDA advisory committee
review, if applicable, based on a determination that the drug is safe and effective for the
proposed indication(s).
Preclinical
tests include laboratory evaluation of product chemistry, toxicity, and formulation, as well as animal studies. The conduct of the preclinical
tests and formulation of the compounds for testing must comply with federal regulations and requirements, including GLP regulations.
The results of the preclinical tests, together with manufacturing information and analytical data, are submitted to the FDA as part of
an IND application, which must become effective before human clinical trials may begin. An IND application will automatically become
effective 30 days after receipt by the FDA, unless before that time the FDA raises concerns or questions about issues such as the conduct
of the trials as outlined in the IND application, and places the clinical trial(s) on a clinical hold. In such a case, the IND application
sponsor and the FDA must resolve any outstanding FDA concerns or questions before clinical trials can proceed. We cannot be certain that
submission of an IND application will result in the FDA allowing clinical trials to begin.
10
Clinical
trials necessary for product approval are typically conducted in three sequential phases, but the Phases may overlap or be combined.
The study protocol and informed consent information for study subjects in clinical trials must also be approved by an IRB for each institution
where the trials will be conducted, and each IRB must monitor the study until completion. Study subjects must provide informed consent
and sign an informed consent form before participating in a clinical trial. Clinical testing also must satisfy the extensive GCP regulations
for, among other things, informed consent and privacy of individually identifiable information.
● Phase
1—Phase 1 clinical trials involve initial introduction of the study drug in a limited
population of healthy human volunteers or patients with the target disease or condition.
These studies are typically designed to test the safety, dosage tolerance, absorption, metabolism
and distribution of the study drug in humans, evaluate the side effects associated with increasing
doses, and, if possible, to gain early evidence of effectiveness.
● Phase
2—Phase 2 clinical trials typically involve administration of the study drug to a limited
patient population with a specified disease or condition to evaluate the preliminary efficacy,
optimal dosages and dosing schedule and to identify possible adverse side effects and safety
risks. Multiple Phase 2 clinical trials may be conducted to obtain information prior to beginning
larger and more expensive Phase 3 clinical trials.
● Phase
3—Phase 3 clinical trials typically involve administration of the study drug to an
expanded patient population to further evaluate dosage, to provide substantial evidence of
clinical efficacy and to further test for safety, generally at multiple geographically dispersed
clinical trial sites. These clinical trials are intended to establish the overall risk/benefit
ratio of the study drug and to provide an adequate basis for product approval. Generally,
two adequate and well-controlled Phase 3 clinical trials are required by the FDA for approval
of an NDA.
Post-approval
trials, sometimes referred to as Phase 4 clinical trials, may be conducted after receiving initial marketing approval. These trials are
used to gain additional experience from the treatment of patients in the intended therapeutic indication and are commonly intended to
generate additional safety data regarding use of the product in a clinical setting. In certain instances, the FDA may mandate the performance
of Phase 4 clinical trials as a condition of approval of an NDA or, in certain circumstances, post-approval.
The
FDA has various programs, including fast track designation, breakthrough therapy designation, priority review and accelerated approval,
which are intended to expedite or simplify the process for the development, and the FDA’s review of drugs ( e.g., approving
an NDA on the basis of surrogate endpoints subject to post-approval trials). Generally, drugs that may be eligible for one or more of
these programs are those intended to treat serious or life-threatening diseases or conditions, those with the potential to address unmet
medical needs for those disease or conditions, and/or those that provide a meaningful benefit over existing treatments. For example,
a sponsor may be granted FDA designation of a drug candidate as a “breakthrough therapy” if the drug candidate is intended,
alone or in combination with one or more other drugs, to treat a serious or life-threatening disease or condition and preliminary clinical
evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant
endpoints, such as substantial treatment effects observed early in clinical development. If a drug is designated as breakthrough therapy,
the FDA will take actions to help expedite the development and review of such drug. Moreover, if a sponsor submits an NDA for a product
intended to treat certain rare pediatric or tropical diseases or for use as a medical countermeasure for a material threat, and that
meets other eligibility criteria, upon approval such sponsor may be granted a priority review voucher that can be used for a subsequent
NDA. From time to time, we anticipate applying for such programs where we believe we meet the applicable FDA criteria. A company cannot
be sure that any of its drugs will qualify for any of these programs, or even if a drug does qualify, that the review time will be reduced.
The
results of the preclinical studies and of the clinical studies, together with other detailed information, including information on the
manufacture and composition of the drug, are submitted to the FDA in the form of an NDA requesting approval to market the product for
one or more proposed indications. The testing and approval process requires substantial time, effort and financial resources. Unless
the applicant qualifies for an exemption, the filing of an NDA typically must be accompanied by a substantial “user fee”
payment to the FDA. To support marketing approval, the data submitted must be sufficient in quality and quantity to establish the safety
and efficacy of the product in the proposed patient population to the satisfaction of the FDA. After an NDA is accepted for filing, the
FDA substantively reviews the application and may deem it to be inadequate, and companies cannot be sure that any approval will be granted
on a timely basis, if at all. The FDA may also refer the application to an appropriate advisory committee, typically a panel of clinicians,
for review, evaluation and a recommendation as to whether the application should be approved, but is not bound by the recommendations
of the advisory committee.
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Before
approving an NDA, the FDA usually will inspect the facility or the facilities at which the drug is manufactured and determine whether
the manufacturing and production and testing facilities are in compliance with cGMP regulations. The FDA also may audit the clinical
trial sponsor and one or more sites at which clinical trials have been conducted to determine compliance with GCPs and data integrity.
If the NDA and the manufacturing facilities are deemed acceptable by the FDA, it may issue an approval letter, and, if not, the Agency
may issue a Complete Response Letter (“CRL”). An approval letter authorizes commercial marketing of the drug with specific
prescribing information for a specific indication(s). A CRL indicates that the review cycle of the application is complete and the application
is not ready for approval. A CRL may require additional clinical data and/or an additional pivotal Phase 3 clinical trial(s), and/or
other significant, expensive and time-consuming requirements related to clinical trials, preclinical studies or manufacturing. Even if
such additional information is submitted, the FDA may ultimately decide that the NDA does not satisfy the criteria for approval. The
FDA could also require, as a condition of NDA approval, post-marketing testing and surveillance to monitor the drug’s safety or
efficacy or impose other conditions, or a REMS that may include both special labeling and controls, known as Elements to Assure Safe
Use, on the distribution, prescribing, dispensing and use of a drug product. Once issued, the FDA may withdraw product approval if, among
other things, ongoing regulatory requirements are not met, certain defects exist in the NDA, or safety or efficacy problems occur after
the product reaches the market.
Intellectual
Property
Information
regarding the issued patents and pending patent applications, as of December 31, 2022, is as follows:
Subject
Matter
Issued
Pending
Geographic
Scope
Patent Term
Qualigen
Patents and Trademarks
FastPack
1.0, IP, and PRO
2
0
U.S.,
Japan
2024-2032
FastPack
2.0
23
0
U.S.,
Europe, China, Japan
2032-2042
STARS
9
6
U.S.,
Europe, Canada, China, Japan, Korea
2030-2045
Qualigen
Trademarks
13
9
U.S.,
Europe, Canada, China, Japan, Korea
N/A
Qualigen
+ Gen-Probe (Joint)
24
0
U.S.,
Austrialia, Canada, China, Japan
2028
Total
Qualigen
71
15
In-Licensed
Patents
FastPack
1.0, IP, and PRO
1
0
Europe
2030
Univ
College London (UCL)
QN-302
2
11
U.S.,
Europe, Australia, Canada, China, Hong Kong, India, Japan, Korea, Russia
2030-2040
Univ
of Louisville (ULRF)
RAS
0
12
U.S,
Europe, Australia, Canada, China, Hong Kong, India, Israel, Japan, Korea, Mexico, Russia, South Africa
2039*
QN-247
44
3
U.S.,
Europe, Canada, China, Hong Kong, Japan
2032-2038
DiaSource
Total
In-Licensed
47
26
TOTAL
118
41
* Anticipated
patent term
Human
Capital Management
As
of March 31, 2023, we had 38 employees, 31 of whom were full-time employees. None of our employees is represented by a labor union or
covered by a collective bargaining agreement.
Employee
Engagement, Benefits & Development. We recognize that attracting, motivating and retaining talent at all levels is vital to our
continued success. Our employees are a significant asset and we aim to create an equitable, inclusive and empowering environment in which
our employees can grow and advance their careers, with the overall goal of developing, retaining and expanding our workforce, as needed,
to support our current pipeline and future business goals. By focusing on employee retention and engagement, we also improve our ability
to support our business and operations, our pipeline, and also protect the long-term interests of our shareholders. We frequently benchmark
our compensation practices and benefits programs against those of comparable companies in our industry and in the geographic area where
we are located. In our efforts to recruit and retain a diverse and exceptional workforce, we provide our employees with competitive cash
compensation, opportunities to own equity, and an employee benefit program that promotes well-being, including healthcare, a 401(k) Plan,
and paid time-off.
Diversity
& Inclusion . Our success also depends on our ability to attract, engage and retain a diverse group of employees. We value diversity
across our workforce and we will continue to focus on diversity and inclusion initiatives. With respect to our employees overall, approximately
fifty percent (50%) are people of color and approximately forty-five percent (45%) are women. We seek to have an inclusive and positive
culture that is centered on our shared corporate mission and values, and that is free from discrimination of any kind, including sexual
or other discriminatory harassment. Our employees have multiple avenues available through which inappropriate behavior can be reported.
All reports of inappropriate behavior are promptly investigated with appropriate action taken to stop such behavior.
Additional
Information
Ritter
Pharmaceuticals, Inc. (our predecessor) was formed as a Nevada limited liability company on March 29, 2004 under the name Ritter Natural
Sciences, LLC. In September 2008, this company converted into a Delaware corporation under the name Ritter Pharmaceuticals, Inc. On May
22, 2020, upon completing the “reverse recapitalization” transaction with Qualigen, Inc., Ritter Pharmaceuticals, Inc. was
renamed Qualigen Therapeutics, Inc. Qualisys Diagnostics, Inc. was formed as a Minnesota corporation in 1996, reincorporated to become
a Delaware corporation in 1999, and then changed its name to Qualigen, Inc. in 2000. Qualigen, Inc. is now a wholly-owned subsidiary
of the Company.
Our
website address is www.qualigeninc.com . We post links to our website to the following filings as soon as reasonably practicable
after they are electronically filed with or furnished to the SEC: annual reports on Form 10-K, quarterly reports on Form 10-Q, current
reports on Form 8-K, proxy statements, information statements, beneficial ownership reports and any amendments to those reports or statements
filed or furnished pursuant to Sections 13(a), 14 or 15(d) of the Securities Exchange Act of 1934, as amended (the “Exchange Act”).
All such filings are available through our website free of charge. However, the information contained on or accessed through our website
does not constitute part of this Annual Report, and references to our website address in this Annual Report are inactive textual references
only. All such reports are also available free of charge via EDGAR through the SEC website at www.sec.gov .
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