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, QN-247 and RAS-F. Our
investigational QN-302 compound is a small molecule G4 selective transcription inhibitor with strong binding affinity to G4s prevalent
in cancer cells. Such binding could, by stabilizing the G4s against “unwinding,” help inhibit cancer cell proliferation.
QN-247 is a DNA coated gold nanoparticle cancer drug candidate that has the potential to target various types of cancer; the nanoparticle
conjugate technology is similar to the core nanoparticle coating technology used in our blood-testing diagnostic products. 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. RAS-F is a family of RAS oncogene protein-protein interaction inhibitor small molecules
for preventing 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. Although we have no ongoing development efforts
for STARS, a DNA/RNA-based therapeutic device product concept for removing precisely targeted tumor-produced and viral compounds
from circulating blood, we are currently identifying strategic partnering opportunities.
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Our
FastPack System diagnostic instruments and test kits 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. We currently use our diagnostics distribution partner
Sekisui Diagnostics, LLC (“Sekisui”) for most FastPack distribution worldwide pursuant to a distribution agreement, but maintain
direct distribution for certain house accounts, including selling our total testosterone test kits to Low T Center, Inc. (“Low
T”), the largest men’s health group in the United States, with 40 locations. The distribution agreement with Sekisui will
expire on March 31, 2022, at which time the services currently provided by Sekisui will revert to us and we will recognize 100% of the
revenue from the sales of our FastPack diagnostic instruments and test kits. We have licensed and technology-transferred our FastPack
System technology to Yi Xin Zhen Duan Jishu (Suzhou) Ltd. for the China diagnostics market.
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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Product Candidates
Therapeutics
and Diagnostics 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. 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 RAS-F portfolio is designed to suppress the interaction of endogenous RAS with
c-RAF, upstream of the KRAS, HRAS and NRAS effector pathways.
Our
Selective Target Antigen Removal System (STARS) is a therapeutic device product concept, currently in discovery stage, designed to remove
circulating tumor cells, viruses, inflammation factors and immune checkpoints.
Our
deprioritized, non-core drug candidate QN-165 (formerly referred to as AS1411, thus not featured in the chart above) is a drug candidate
for the potential broad-spectrum treatment of infectious diseases such as COVID-19.
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 G4 binding concept is derived from over 30 years in nucleic acid research, including
that of G4s, which are higher order DNA and RNA structures formed by sequences containing guanine-rich repeats. G4s are overrepresented
in telomeres 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 those cancer genes which have a high prevalence
of enriched G4s in a process that can be predicted by bioinformatics. 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 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. This has been supported by in-vitro
and in-vivo studies that have shown that G4 stabilization by QN-302 results in inhibition of target gene expression and cessation of
cell growth in a variety of G4 prevalent cancers, including pancreatic ductal adenocarcinoma (“PDAC”) which represents 98%
of pancreatic cancers.
Pancreatic
cancer is the tenth most common cancer and fifth deadliest cancer in the United States and has one of the lowest rates of survival of
all cancer types, with 98% 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 PDAC compared to existing agents, with a distinct mechanism of action and preclinical target profile.
In
vitro studies show QN-302 potently inhibits the growth of several PDAC cell lines at low nM concentrations. Likewise, QN-302 shows longer
survival duration in a KPC genetic mouse model for pancreatic cancer than gemcitabine has historically shown. Additional preclinical
studies suggest activity in gemcitabine resistant PDAC. Data from therapy studies on three patient-derived PDAC xenografts indicated
that QN-302 had significant anti-tumor activity in PDAC. Early safety indicators suggest no adverse toxic effects at proposed therapeutic
doses in pancreatic cancer in-vivo models.
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We
plan to seek to obtain Orphan Drug status for QN-302 for one or more indications, such as PDAC. Orphan Drug status, if obtained, would
be expected to confer advantages that may include faster regulatory review and increased market protection.
QN-247
(formerly referred to as ALAN or AS1411-GNP)
QN-247
is an aptamer-based drug candidate that is designed to treat different types of cancer, including liquid and solid tumors. QN-247 inhibits
nucleolin, a key multi-functional regulatory protein that is overexpressed in cancer cells; QN-247 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.
A
key component of this drug candidate, DNA 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 side effects, with at least seven patients
appearing to have long-lasting clinical responses where their cancers disappeared or shrank substantially. (QN-165 may also be useful
against infectious diseases – see below.)
QN-247
is an enhanced version of QN-165 (which in turn was formerly referred to as AS1411) where the DNA aptamer is attached to a gold nanoparticle.
In
a Qualigen-sponsored University of Louisville (“UofL”) in-vitro preclinical study involving tumor-associated macrophages,
QN-247 was shown to have stronger anti-cancer activity than QN-165 alone did. Tumor-associated macrophages are a class of immune cells
present in high numbers around solid tumors and affect most aspects of tumor cell biology; they drive pathological phenomena including
tumor cell proliferation, tumor angiogenesis, invasion and metastasis, immunosuppression, and drug resistance. In most cancers, the tumor-associated
macrophages have an M2 phenotype, which may inhibit the anti-tumor effects of immune checkpoint inhibitor drugs, such as Merck’s
Keytruda (pembrolizumab). We believe that converting these M2 macrophages to the M1 phenotype could enhance the activity of these immune
checkpoint inhibitors. In the UofL study, QN-247 increased the conversion of M2 macrophages to the M1 phenotype, while also reducing
the overall proliferation of macrophages.
A
UofL in-vitro preclinical study with triple negative breast cancer cells (MDA-MB-231) indicated that QN-247, in combination with radiation
therapy, resulted in reduced tumor cell colony size ( i.e ., resulted in increased tumor cell necrosis) compared to radiation alone.
We
plan to seek to obtain Orphan Drug status for QN-247 for one or more indications, such as pancreatic cancer, AML and pediatric neuroblastoma.
Orphan Drug status, if obtained, would be expected to confer advantages that may include faster regulatory review and increased market
protection.
In October 2020,
we entered into an amended sponsored research agreement with UofL to advance development of our QN-247 drug candidate. The work being
performed under the original sponsored research agreement, entered into in August 2018, comprises animal studies to assess antitumor
efficacy and safety of different QN-247 compositions designed to treat pediatric and adult AML. Under the amended sponsored research
agreement, UofL is performing preclinical studies on AML and on additional indications including glioblastoma, a malignant brain cancer
that is difficult to treat because most drugs cannot pass the blood-brain membrane, and non-small cell lung cancer, which comprises approximately
85% of the 1.6 million global lung cancer cases each year. Additionally, we and UofL will study how QN-247 may inhibit metastasis
of cancer cells as a potential adjuvant therapy.
RAS-F
In
July 2020, we entered into an exclusive worldwide license agreement with UofL for the intellectual property covering the “RAS-F”
family of RAS oncogene protein-protein interaction inhibitor small molecule drug candidates, which would work by blocking RAS mutations
directly and thereby inhibiting tumor formation (especially in pancreatic, colorectal and lung cancers). Pursuant to the license agreement,
we in-licensed the “RAS-F” 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 protein-protein interaction inhibitor licensed products.
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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 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. There is currently no FDA-approved direct RAS protein inhibitor
available. Drugs that target signaling downstream of RAS are available; however, such drugs have shown disappointing clinical activity
because RAS is a “hub” that activates multiple effectors, so drugs that block a single pathway downstream do not account
for the many other activated pathways.
In
March 2022, we signed an amendment to our active sponsored research agreement with UofL to extend our partnership. Under the revised
agreement, the collaboration extends until the first quarter of 2023 and commits additional resources to support ongoing discovery and
preclinical efforts for the RAS-F platform.
STARS ™
Our
FastPack diagnostic system and related core technologies are now the basis for potential blood-filtering therapeutic applications for
the treatment of cancer and infectious disease. Our Selective Target Antigen Removal System (“STARS”) therapeutic
device concept is intended to utilize core expertise in advanced reagents and coatings to remove disease associated agents, including
viruses and tumor-produced compounds, directly from a patient’s blood. The key components of STARS, membranes coated with target
capture reagents, will utilize several proprietary processes developed and used in the FastPack product lines. Proprietary STARS cartridges
are expected to be designed for use with conventional dialysis or hemofiltration machines to remove immune checkpoints, metastatic cells
and inflammation factors from cancer patients’ bloodstreams. We believe STARS may also be able to be developed to treat infectious
diseases, by removing circulating viruses sufficiently to facilitate patient stabilization and recovery. Although
we have no ongoing development efforts for STARS, we are currently identifying strategic partnering opportunities.
In
August 2020, the United States Patent and Trademark Office issued to us patent No. 10,744,258 entitled “Devices and Methods for
On-Line Whole Blood Treatment” regarding our STARS technology.
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 United States 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 filed an Investigational New Drug (“IND”) application with the U.S. Food and Drug Administration (“FDA”)
to seek approval to commence Phase 1b/2a clinical studies with QN-165 in hospitalized COVID-19 patients. On August 11, 2021,
the FDA informed us that additional preclinical studies would be required in order for such application to be cleared. There can be no
assurance when (if ever) the FDA would clear this IND application or any other IND application we may file. We have decided to deprioritize
the QN-165 program as our therapeutics strategy is focused on oncology.
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 $120 million. We manufacture the FastPack products at our FDA and International Standards Organization (“ISO”)
certified Carlsbad, California facility. We maintain direct distribution for certain house accounts, including Low T, but pursuant to
a distribution agreement, our diagnostics distribution partner Sekisui holds most FastPack distribution rights until March 31, 2022,
after which time we will resume full commercial responsibility.
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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
As
of January 2022, we have entered into a royalty-bearing license agreement with UCL, including intellectual property and know-how covering
lead and backup compounds for our G4 selective transcription inhibitor program, QN-302.
We
have entered into a royalty-bearing license agreement for key components of QN-247 from UofL and we have commissioned sponsored research
from UofL’s development teams in order to optimize and prepare QN-247 for human trials. A separate team at UofL, funded by us under
a sponsored research agreement, is developing RAS-F. We have an active royalty-bearing license agreement for the RAS-F program as well.
In
2016, we entered into an agreement with Sekisui, whereby Sekisui distributes our diagnostic product line worldwide. As described above,
this distribution agreement will expire on March 31, 2022.
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.
We
had exclusive rights to the core QN-165 aptamer from Advanced Cancer Therapeutics, LLC; this agreement terminated on March 1, 2022.
Sales
Channels
We
currently sell our FastPack diagnostic product line primarily through our distribution partner Sekisui under a distribution agreement
whereby Sekisui receives a portion of sales revenue. In the United States, Sekisui commercializes the FastPack product line through its
own direct sales force and distribution agreements with 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, Sekisui commercializes the FastPack product line through a network of distributors in Europe, Asia, Middle East, and North
Africa. Our distribution agreement with Sekisui will expire on March 31, 2022, at which time the
services currently provided by Sekisui will revert to us and we will recognize 100% of the revenue from the sales of our FastPack diagnostic
instruments and test kits. Once the distribution agreement expires, we do not expect any interruption to our diagnostics sales and marketing
engine as we will continue to leverage established partnerships with our various distributors in both the United States and abroad.
In
addition, among our other direct sales accounts, we currently sell FastPack products directly to Low T. Sales to Sekisui accounted for
62% of our total revenues during the fiscal year ended December 31, 2021, and sales to Low T accounted for 22% of our total revenues
during this period. The remaining revenue was comprised of warranties and product sales to our other direct sales accounts as well as
license revenues.
In
October 2020, we entered into an agreement with Yi Xin Zhen Duan Jishu (Suzhou) Ltd (“Yi Xin”), pursuant to which Yi Xin
obtained 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 would be entitled to receive royalties on any such sales.
After May 1, 2022, Yi Xin will have 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 will also have the right
to sell Yi Xin-manufactured versions of our existing FastPack 1.0, IP and PRO product lines. We would be entitled to receive royalties
on any of these sales, as well. After March 31, 2022, Yi Xin will have 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.
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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 Thermo Fisher Scientific, Equitech-Bio, Surmodics, OYC Americas, Amcor, 3M, VWR,
Gilson, Impact Project Management, Enstrom, Hi-Tech Products, and Hamamatsu.
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 in the cancer and infectious disease fields. We would engage contract research organizations for any clinical trials
of our drug candidates. We intend to focus our internal research and development on 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.
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.
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In
the European Union (“EU”), we are required to comply with the Medical Device Regulation (“MDR” or “EU
MDR”), which became effective May 2021, superseding existing Medical Device Directives. Medical devices that have a
valid CE Certificate to the prior Directives (issued before May 2021) can continue to be sold until May 2024 or until the CE 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 MDR. The MDR
changes multiple aspects of the regulatory framework for CE marking, such as increased clinical evidence requirements, changes to labelling,
and new requirements, including Unique Device Identification (“UDI”), and many new post-market reporting obligations. MDR
also modifies and increases the compliance requirements for the medical device industry and will continue to require significant investment
over the next few years to transition all products by May 2024. 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. Regulatory requirements are becoming more stringent, with the China National Medical Product Administration
(“NMPA”) recently increasing the regulatory requirements to market and maintain products in China, and the introduction of
such regulatory requirements in many countries in the Middle East and Southeast Asia that previously did not have medical device regulations,
or had minimal regulations. As a result of the United Kingdom’s departure from the EU, we also expect a U.K. Regulation
to be implemented beginning July 2023, with requirements to sell in the U.K. already in place including appointment of a U.K. Responsible
Person and device registration with The Medicines and Healthcare products Regulatory Agency (“MHRA”). In addition, other
EU countries continue to impose significant local registration requirements despite the implementation of MDR.
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,
such as China, for example, 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.
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;
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● 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.
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.
11
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.
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
We
currently maintain a portfolio of 147 issued, allowed, in-licensed or pending patents, patent applications and provisional patent applications
covering various aspects of our products and product candidates in the United States, Canada, Mexico, Europe, Japan, China, Korea, Israel,
South Africa, and Australia. In addition, we have seven issued and 28 pending trademark registrations in the United States pertaining
to our diagnostics and therapeutics businesses. There are currently no contested proceedings or third party claims against any Qualigen
intellectual property.
Within
our diagnostics patent portfolio, we hold two issued patents covering FastPack 1.0, IP and PRO and 23 issued patents covering FastPack
2.0. In addition, we in-licensed one issued patent covering our Vitamin D assay from DIAsource ImmunoAssays S.A.. We also, with Gen-Probe
Incorporated, hold 24 issued joint patents covering FastPack Molecular, an inactive product program. Last, we hold five issued patents
and 10 patents-pending covering our development-stage STARS theranostic system.
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Within
our therapeutics patent portfolio, we have 43 issued and 11 patents-pending, including patent applications, covering the QN-247 program
set to expire 2032-2038. In addition, we have two patent applications covering the QN-165 program and 15 pending patents covering the
RAS program. All 71 patents, pending patents and applications covering QN-247, QN-165, and RAS are in-licensed from ULRF. Finally, we
exclusively in-licensed 11 patents, two of which are issued, from UCL covering our QN-302 program and set to expire 2030-2033.
Human
Capital Management
As
of March 25, 2022, we had 46 employees, 39 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 believe that our future success is dependent upon our ability to recruit, hire and retain
exceptional employees. We frequently benchmark our compensation practices and benefits programs
against those of comparable industries and in the geographic area where our facility is located. 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 with matching contributions, and paid time-off. The
success of our business is fundamentally connected to the well-being, health and safety of our employees. In an effort to protect the
health and safety of our employees, we took proactive action from the earliest signs of the COVID-19 outbreak, which included implementing
social distancing policies at our facilities, facilitating remote working arrangements and imposing employee travel restrictions.
Diversity
& Inclusion . We value diversity across our workforce and we will continue to focus on diversity and inclusion initiatives. 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.