Item 1. Business
Item
1. Business
Overview
We
are an early-clinical-stage therapeutics company focused on developing treatments for adult and pediatric cancer. Our business now consists
of one early-clinical-stage therapeutic program (QN-302) and one preclinical therapeutic program (Pan-RAS).
Our
lead 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 as pancreatic cancer). Such binding could, by stabilizing the G4s against DNA
“unwinding,” help inhibit cancer cell proliferation. QN-302 is currently undergoing a Phase 1a clinical trial at START
Midwest in Grand Rapids, Michigan, and HonorHealth in Scottsdale, Arizona.
Our
Pan-RAS program, which is currently at the preclinical stage, 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 thereby
leaving the proteins from the mutated RAS unable to cause further harm. In theory, such mechanism of action may be effective in the treatment
of about one quarter of all cancers, including certain forms of pancreatic, colorectal, and lung cancers .
The investigational compounds within our Pan-RAS portfolio are designed to suppress the interaction of endogenous RAS with c-RAF,
upstream of the KRAS, HRAS and NRAS effector pathways.
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. O n
July 20, 2023, we sold our Qualigen, Inc. subsidiary, which contained our former FastPack ® diagnostics business to Chembio
Diagnostics, Inc., an American subsidiary of French diagnostics provider Biosynex, S.A. Accordingly, our former FastPack ®
diagnostics business is reported as Discontinued Operations in this Annual Report.
The
aggregate net purchase price for Qualigen, Inc. was $5.4 million in cash, of which $450,000 is being held in escrow to satisfy certain
Company indemnification obligations. Any amounts remaining in the escrow that have not been offset or reserved for claims will be released
to us within five business days following January 20, 2025.
We
own a minority interest in NanoSynex, Ltd. (“NanoSynex”), a privately-held microbiologics diagnostic company domiciled in
Israel. NanoSynex’s technology is for Antimicrobial Susceptibility Testing 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. On May 26, 2022, we acquired a 52.8% interest in NanoSynex from our related party Alpha Capital Anstalt (“Alpha”)
and NanoSynex, and entered into a Master Agreement for the Operational and Technological Funding of NanoSynex with NanoSynex (the “NanoSynex
Funding Agreement”). On July 20, 2023, we entered into an Amendment and Settlement Agreement with NanoSynex (the “NanoSynex
Amendment”), pursuant to which we agreed to, in exchange for eliminating all future Funding Agreement obligations for us to invest
further cash in NanoSynex (except for obligations to lend NanoSynex $560,000 on or before November 30, 2023, and $670,000 on or before
March 31, 2024), surrender 281,000 Series B Preferred Shares of NanoSynex held by us, resulting in our ownership in NanoSynex being reduced
from approximately 52.8% to approximately 49.97% of the voting equity of NanoSynex; in addition, we agreed to surrender approximately
$3.0 million of promissory notes which NanoSynex had issued to us under the Funding Agreement. On November 22, 2023 we further agreed
to eliminate our obligations to lend NanoSynex $560,000 on or before November 30, 2023, and $670,000 on or before March 31, 2024, by
instead surrendering shares of Series A-1 Preferred Stock of NanoSynex in an amount that reduced our ownership in NanoSynex voting equity
from approximately 49.97% to 39.90%. NanoSynex was deconsolidated from our financial statements as of July 20, 2023, and is reported
as Discontinued Operations in this Annual Report. Our investment in NanoSynex will be accounted for in the future as an equity method
investment.
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Product
Pipeline
QN-302
We
exclusively in-licensed the global rights to the G-Quadruplex (“G4”) selective transcription inhibitor platform from University
College London (“UCL”) in January 2022. The licensed technology comprises lead compound QN-302 (formerly known as 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 nucleic acid research conducted over more
than over 30 years, 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.
We
believe that QN-302 has the potential to demonstrate superior efficacy and activity against pancreatic ductal adenocarcinoma (“PDAC”),
which represents 98% of pancreatic cancers. Pancreatic cancer is the tenth most common cancer in men and the seventh most common in women,
but it is the fourth leading cause of cancer deaths in men and the third leading cause in women; it accounts for about 3% of all cancers
in the United States but is responsible for about 8% of all cancer-related deaths. It has one of the lowest rates of survival of all
cancer types.
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. 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 (the current standard of care for PDAC) 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 in pancreatic cancer mouse in-vivo models
suggest no significant adverse toxic effects at proposed therapeutic doses.
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.
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.
On
August 1, 2023 we announced that the FDA had cleared our investigational new drug (“IND”) application for QN-302, and on
November 1, 2023 the first patient in our Phase 1a clinical trial for QN-302 was dosed at START Midwest in Grand Rapids, Michigan.
We
will require additional cash resources to be able to continue and complete this Phase 1a clinical trial.
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Pan-RAS
(formerly referred to as RAS or RAS-F)
In
July 2020 we entered into an exclusive worldwide in-license agreement with the University of Louisville’s Research Foundation (“UofL”
or “ULRF”) 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 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 Pan-RAS inhibitor licensed
products. The license agreement with UofL for Pan-RAS was amended in March 2021 and June 2023.
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.
We
also had a sponsored research agreement with UofL for Pan-RAS research; that agreement expired in December 2023.
We
currently do not have the resources to advance our Pan-RAS program, and so we are seeking to out-license it.
On
February 15, 2024, we entered into a License and Sublicense Agreement with Pan-RAS Holdings, Inc., a New York corporation (“Pan-RAS
Holdings”), which contemplated an exclusive out-license of our Pan-RAS drug development program, including our rights under the
ULRF license agreement, Pan-RAS Holdings.
Although
the License and Sublicense Agreement called for a closing by March 16, 2024, the License and Sublicense Agreement was in essence structured
as a 30-day option in favor of Pan-RAS Holdings.
At
the contemplated closing, Pan-RAS Holdings would have paid us an upfront fee of $1,000,000 in cash. In addition, Pan-RAS Holdings would
have become responsible to pay on our behalf our in-license royalty obligations to ULRF, as and when required.
Finally,
if the contemplated closing had occurred, Pan-RAS Holdings would have required to pay to us for our own account, on a semiannual basis,
royalties equal to 1.0% of net sales of any RAS products.
We
would have owed certain amounts to ULRF under our in-license agreement from them, if, as and when we received any Non-Royalty Sublicensing
Income from Pan-RAS Holdings.
Pan-RAS
Holdings did not effectuate the closing by March 16, 2024, and we and they voluntarily terminated the License and Sublicense Agreement
effective as of March 16, 2024.
Previous
Programs
We
have discontinued all of our efforts the following programs, and we do not plan to resume them:
1.
QN-247(formerly
referred to as ALAN or AS1411-GNP) – an oligonucleotide aptamer-based, nucleolin-inhibiting anticancer drug candidate,
consisting of QN-165 conjugated with gold nanoparticles.
2.
QN-165
(formerly referred to as AS1411) – an oligonucleotide aptamer-based drug candidate for the potential broad-spectrum
treatment of infectious diseases such as COVID-19.
3.
Selective
Target Antigen Removal System (STARS) – a therapeutic blood-filtering device product concept, which would be designed
to remove circulating tumor cells, viruses, inflammation factors and immune checkpoints.
Research
and Development
For
research and development of our drug candidates, we have historically leveraged the scientific and technical resources and laboratory
facilities of UofL and UCL, through technology licensing, sponsored research, and other consulting agreements. We have engaged contract
research organizations (“CROs”) and clinical sites for the Phase 1a clinical trial of QN-302. We intend to focus our internal
research and development on oversight of these CROs. We currently have no internal research and development facilities.
Regulatory
Matters
We
have obtained FDA clearance/approval for our QN-302 Phase 1a clinical trial. We have not obtained FDA or other regulatory approval for
any other drug candidate.
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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 Food, Drug and Cosmetics Act 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;
●
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; 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.
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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, 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 Risk Evaluation and Mitigation Strategy 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 our (in-licensed) issued patents and pending patent applications, as of December 31, 2023, is as follows (excluding patents
and pending patent applications which pertain to programs which we have discontinued). As of that date we did not have any directly-owned
issued patents and pending patent applications.
Subject
Matter
Issued
Pending
Geographic
Scope
Patent
Term
In-Licensed
Patents
University
College London (UCL)
QN-302
3
10
U.S.,
Europe, Australia, Canada, China, Hong Kong, India, Japan, Korea, Russia
2030-2040
University
of Louisville (ULRF)
Pan-RAS
0
12
U.S.,
Europe, Australia, Canada, China, Hong Kong, India, Israel, Japan, Korea, Mexico, Russia, South Africa
2039*
TOTAL
3
22
* Anticipated
patent term
Human
Capital Management
As
of March 25, 2024, we had 4 employees, all of whom were full-time. None of our employees
is represented by a labor union or covered by a collective bargaining agreement.
Diversity
& Inclusion . With respect to our employees overall, fifty percent (50%) are women and 0% are people of color.
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. and Qualigen, Inc. became a wholly-owned subsidiary of the Company. On July 20, 2023 we sold Qualigen
Inc. to ChemBio Diagnostics, Inc., an American subsidiary of French diagnostics provider Biosynex S.A.
Our
website address is www.qlgntx.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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