10-K
1
f10k2020_soligenix.htm
ANNUAL REPORT
UNITED
STATES SECURITIES AND EXCHANGE COMMISSION
Washington,
D.C. 20549
FORM
10-K
(Mark
One)
☒
ANNUAL REPORT UNDER SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934.
For
the Fiscal Year Ended December 31, 2020
☐
TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934.
For
the transition period from ____________ to ____________
Commission
File No. 000-16929
SOLIGENIX,
INC.
(Exact
name of registrant as specified in its charter)
29 EMMONS DRIVE, SUITE B-10 PRINCETON, NJ 08540
(Address of principal executive offices) (Zip Code)
(Registrant’s
telephone number, including area code)
Securities
registered under Section 12 (b) of the Exchange Act:
Title of each class Trading Symbol (s) Name of each exchange on which registered
Common Stock, par value $0.01 per share SNGX The Nasdaq Capital Market
Common Stock Purchase Warrants SNGXW The Nasdaq Capital Market
Securities
registered under Section 12(g) of the Exchange Act: None
Indicate
by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Yes ☐ No
☑
Indicate
by check mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act. Yes ☐
No ☑
Indicate
by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities
Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such
reports), and (2) has been subject to such filing requirements for the past 90 days. Yes ☑
No ☐
Indicate
by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted pursuant
to Rule 405 of Regulation S-T (§232.405 of this chapter) during the preceding 12 months (or for such shorter period that
the registrant was required to submit such files). Yes ☑ No ☐
Indicate
by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, or a smaller
reporting company. See the definition of “large accelerated filer”, “accelerated filer” and “smaller
reporting company” in Rule 12b-2 of the Exchange Act. (Check one):
Large accelerated filer ☐ Accelerated filer ☐
Non-accelerated filer ☒ Smaller reporting company ☒
Emerging growth company ☐
If
an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for
complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
Indicate by check
mark whether the registrant has filed a report on and attestation to its management’s assessment of the effectiveness of
its internal control over financial reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered
public accounting firm that prepared or issued its audit report. ☐
Indicate
by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act). Yes ☐ No ☑
The aggregate market value of the common stock held by non-affiliates
of the registrant was $57,299,617 (assuming, for this purpose, that executive officers, directors and holders of 10% or more of
the common stock are affiliates), based on the closing price of the registrant’s common stock as reported on The Nasdaq Capital
Market on June 30, 2020.
On
March 23, 2021, there were 40,020,461 shares of the registrant’s common stock outstanding.
DOCUMENTS
INCORPORATED BY REFERENCE: None.
SOLIGENIX,
INC.
ANNUAL
REPORT ON FORM 10-K
For
the Year Ended December 31, 2020
Table
of Contents
Item Description Page
Cautionary Note Regarding Forward-Looking Statements ii
Part I
1. Business 1
1A. Risk Factors 27
1B. Unresolved Staff Comments 48
2. Properties 48
3. Legal Proceedings 48
Part II
6. Selected Financial Data 50
8. Financial Statements and Supplementary Data 57
9A. Controls and Procedures 58
9B. Other Information 58
Part III
10. Directors, Executive Officers and Corporate Governance 59
11. Executive Compensation 64
13. Certain Relationships and Related Transactions and Director Independence 70
14. Principal Accountant Fees and Services 71
Part IV
15. Exhibits and Financial Statement Schedules 72
Signatures 75
Consolidated Financial Statements F-1
i
Cautionary
Note Regarding Forward-Looking Statements
This
Annual Report on Form 10-K contains forward-looking statements, within the meaning of the Private Securities Litigation Reform
Act of 1995, that reflect our current expectations about our future results, performance, prospects and opportunities. These forward-looking
statements are not guarantees of future performance and are subject to significant risks, uncertainties, assumptions and other
factors, which are difficult to predict and may cause actual results to differ materially from those expressed in, or implied
by, any forward-looking statements. The forward-looking statements within this report may be identified by words such as “believes,”
“anticipates,” “expects,” “intends,” “may,” “would,” “will”
and other similar expressions. However, these words are not the exclusive means of identifying these statements. Statements that
are not historical facts are based on our current expectations, beliefs, assumptions, estimates, forecasts and projections for
our business and the industry and markets related to our business and are forward-looking statements.
Actual
outcomes and results may differ materially from what is expressed in such forward-looking statements. Important factors which
may affect these actual outcomes and results include, without limitation:
● maintenance and progression of our business strategy;
Except
as expressly required by the federal securities laws, we undertake no obligation to publicly update or revise any forward-looking
statements to reflect events or circumstances occurring subsequent to the filing of this Form 10-K with the U.S. Securities and
Exchange Commission (“the SEC”) or for any other reason. You should carefully review and consider the various disclosures
we make in this report and our other reports filed with the SEC that attempt to advise interested parties of the risks, uncertainties
and other factors that may affect our business.
ii
PART
I
Item
1. Business
This
Annual Report on Form 10-K contains statements of a forward-looking nature relating to future events or our future financial performance.
These statements are only predictions and actual events or results may differ materially. In evaluating such statements, you should
carefully consider the various factors identified in this report that could cause actual results to differ materially from those
indicated in any forward-looking statements, including those set forth in “Risk Factors” in this Annual Report on
Form 10-K. See “Cautionary Note Regarding Forward Looking Statements.”
Our
Business Overview
We
are a late-stage biopharmaceutical company focused on developing and commercializing products to treat rare diseases where there
is an unmet medical need. We maintain two active business segments: Specialized BioTherapeutics and Public Health Solutions.
Our
Specialized BioTherapeutics business segment is developing and moving toward potential commercialization of SGX301 (synthetic
hypericin) as a novel photodynamic therapy utilizing safe visible light for the treatment of cutaneous T-cell lymphoma (“CTCL”).
With a successful Phase 3 study completed, regulatory approval is being sought and commercialization activities for this product
candidate are being advanced initially in the United States (“U.S.”) Development programs in this business segment
also include our first-in-class innate defense regulator (“IDR”) technology, dusquetide (SGX942) for the treatment
of inflammatory diseases, including oral mucositis in head and neck cancer, and proprietary formulations of oral beclomethasone
17,21-dipropionate (“BDP”) for the prevention/treatment of gastrointestinal (“GI”) disorders characterized
by severe inflammation including pediatric Crohn's disease (SGX203) and acute radiation enteritis (SGX201).
Our
Public Health Solutions business segment includes active development programs for RiVax®, our ricin toxin vaccine
candidate and SGX943, our therapeutic candidate for antibiotic resistant and emerging infectious disease and our vaccine programs
targeting filoviruses (such as Marburg and Ebola) and CiVaxTM, our vaccine candidate for the prevention of COVID-19
(caused by SARS-CoV-2). The development of our vaccine programs incorporates the use of our proprietary heat stabilization platform
technology, known as ThermoVax®. To date, this business segment has been supported with government grant and contract
funding from the National Institute of Allergy and Infectious Diseases (“NIAID”), the Biomedical Advanced Research
and Development Authority (“BARDA”) and the Defense Threat Reduction Agency (“DTRA”).
An outline of our business strategy follows:
1
● Acquire or in-license new clinical-stage compounds for development.
Corporate Information
We
were incorporated in Delaware in 1987 under the name Biological Therapeutics, Inc. In 1987, we merged with Biological Therapeutics,
Inc., a North Dakota corporation, pursuant to which we changed our name to “Immunotherapeutics, Inc.” We changed our
name to “Endorex Corp.” in 1996, to “Endorex Corporation” in 1998, to “DOR BioPharma, Inc.”
in 2001, and finally to “Soligenix, Inc.” in 2009. Our principal executive offices are located at 29 Emmons Drive,
Suite B-10, Princeton, New Jersey 08540 and our telephone number is (609) 538-8200.
Our
Product Candidates in Development
The
following tables summarize our product candidates under development:
Specialized
BioTherapeutics Product Candidates*
Soligenix Product Candidate Therapeutic Indication Stage of Development
2
Public
Health Solutions*†
SGX943 Therapeutic against Emerging Infectious Diseases Pre-clinical
CiVaxTM Vaccine against COVID-19 Pre-clinical
* Timelines subject to potential disruption due to COVID-19 outbreak.
Specialized
BioTherapeutics Overview
SGX301
– for Treating Cutaneous T-Cell Lymphoma
SGX301
is a novel, first-in-class, photodynamic therapy that utilizes safe visible light for activation. The active ingredient in SGX301
is synthetic hypericin, a photosensitizer which is topically applied to skin lesions and then activated by visible fluorescent
light 18 to 24 hours later. Hypericin is also found in several species of Hypericum plants, although the drug used in SGX301
is chemically synthesized by a proprietary manufacturing process and not extracted from plants. Importantly, hypericin is optimally
activated with visible light thereby avoiding the negative consequences of ultraviolet light, and enabling deeper penetration
of the light energy and activation of hypericin. Other light therapies using UVA or UVB light can result in serious adverse effects
including secondary skin cancers.
Combined
with photoactivation, in clinical trials synthetic hypericin has demonstrated significant anti-proliferative effects on activated
normal human lymphoid cells and inhibited growth of malignant T-cells isolated from CTCL patients. In both settings, it appears
that the mode of action is an induction of cell death in a concentration as well as a light dose-dependent fashion. These effects
appear to result, in part, from the generation of singlet oxygen during photoactivation of hypericin.
Hypericin
is one of the most efficient known generators of singlet oxygen, the key component for phototherapy. The generation of singlet
oxygen induces necrosis and apoptosis in adjacent cells. The use of topical synthetic hypericin coupled with directed visible
light results in generation of singlet oxygen only at the treated site. We believe that the use of visible light (as opposed to
cancer-causing ultraviolet light) is a major advance in photodynamic therapy. In a published Phase 2 clinical study in CTCL, after
six weeks of twice weekly therapy, a majority of patients experienced a statistically significant (p<0.04) improvement
with SGX301 whereas the placebo was ineffective: 58.3% compared to 8.3%, respectively.
3
SGX301 has received Orphan Drug
designation as well as Fast Track designation from the FDA. The Orphan Drug Act is intended to assist and encourage
companies to develop safe and effective therapies for the treatment of rare diseases and disorders. In addition to providing
a seven-year term of market exclusivity for SGX301 upon final FDA approval, Orphan Drug designation also positions us to be
able to leverage a wide range of financial and regulatory benefits, including government grants for conducting clinical
trials, waiver of FDA user fees for the potential submission of a NDA for SGX301, and certain tax credits. In addition, Fast
Track is a designation that the FDA reserves for a drug intended to treat a serious or life-threatening condition and one
that demonstrates the potential to address an unmet medical need for the condition. Fast Track designation is designed to
facilitate the development and expedite the review of new drugs. For instance, should events warrant, we will be eligible to
submit a NDA for SGX301 on a rolling basis, permitting the FDA to review sections of the NDA prior to receiving the complete
submission. Additionally, NDAs for Fast Track development programs ordinarily will be eligible for priority review. SGX301
for the treatment of CTCL also was granted Orphan Drug designation from the EMA Committee for Orphan Medical Products and
Promising Innovative Medicine (“PIM”) designation from the Medicines and Healthcare Products Regulatory Agency
(“MHRA”) in the United Kingdom (“UK”).
In
August 2018, the U.S. Patent Office granted us a patent titled “Systems and Methods for Producing Synthetic Hypericin”
for the unique proprietary process manufacturing the highly purified form of synthetic hypericin, the active pharmaceutical ingredient
in SGX301.
In
October 2019, the U.S. Patent Office allowed the divisional patent application titled “Systems and Methods for Producing
Synthetic Hypericin”. The allowed claims are directed to unique, proprietary methods to produce a novel, highly purified
form of synthetic hypericin. This new divisional claim set expands on the previous issued claims in the parent U.S. patent.
In
April 2020, the European patent office granted the divisional patent application titled “Formulations and Methods of Treatment
of Skin Conditions” (No. 2932973). The granted claims are directed to the therapeutic use of synthetic hypericin in the
treatment of CTCL. This new patent expands on our comprehensive patent estate, which includes protection on the composition of
the purified synthetic hypericin, methods of synthesis and therapeutic methods of use in both CTCL and psoriasis, and is being
pursued worldwide.
Based
on the positive and previously published Phase 2 results, we initiated our pivotal Phase 3 clinical study of SGX301 for the treatment
of CTCL during December 2015 and completed the trial in 2020. This trial, referred to as the “FLASH” study (Fluorescent
Light Activated Synthetic Hypericin), aims to evaluate the response to SGX301 as a skin directed therapy
to treat early stage CTCL. We have completed the study with approximately 35 CTCL centers across the U.S. participating in this
pivotal trial. The Phase 3 protocol was a highly powered, double-blind, randomized, placebo-controlled, multicenter trial that
enrolled 169 subjects (166 evaluable). The trial consisted of three treatment cycles, each of eight weeks duration. Treatments
were administered twice weekly for the first six weeks and treatment response was determined at the end of the eighth week. In
the first treatment cycle, approximately 66% of subjects received SGX301 and 33% received placebo treatment of their index lesions.
In the second cycle, all subjects received SGX301 treatment of their index lesions, and in the third cycle, all subjects received
SGX301 treatment of all of their lesions. The majority of subjects enrolled to date have elected to continue into the third optional,
open-label cycle of the study. Subjects were followed for an additional six months after their last evaluation visit. The primary
efficacy endpoint was assessed on the percentage of patients in each of the two treatment groups (i.e., SGX301 and placebo) achieving
a partial or complete response of the treated lesions, defined as a ≥ 50% reduction in the total Composite Assessment of Index
Lesion Disease Severity (“CAILS”) score for three index lesions at the Cycle 1 evaluation visit (Week 8) compared
to the total CAILS score at baseline. Other secondary measures assessed treatment response including duration, degree of improvement,
time to relapse and safety. We continue to work closely with the Cutaneous Lymphoma Foundation, as well as the National Organization
for Rare Disorders.
During
September 2017, the National Cancer Institute (“NCI”), part of the National Institutes of Health (“NIH”)
awarded us a Small Business Innovation Research (“SBIR”) grant of approximately $1.5 million over two years to support
the conduct of our pivotal, Phase 3, randomized, double-blind, placebo-controlled study evaluating SGX301 (synthetic hypericin)
as a treatment for CTCL. This grant was exhausted as of December 2019.
During
October 2018, an Independent Data Monitoring Committee (“DMC”) completed an unblinded interim analysis with data from
approximately 100 subjects, including an assessment of the Phase 3 FLASH study’s primary efficacy endpoint. The DMC provided
a positive recommendation to randomize approximately 40 additional subjects into the trial to maintain the rigorous assumption
of 90% statistical power for the primary efficacy endpoint. No safety concerns were reported by the DMC based on the interim analysis.
4
Positive
primary endpoint analysis for the Phase 3 study for SGX301 was completed in March 2020. The study enrolled 169 patients (166 evaluable)
randomized 2:1 to receive either SGX301 (116 patients) or placebo (50 patients) and demonstrated a statistically significant treatment
response (p=0.04) in the CAILS primary endpoint assessment at 8 weeks for Cycle 1. A total of 16% of the patients receiving SGX301
achieved at least a 50% reduction in their index lesions compared to only 4% of patients in the placebo group at 8 weeks. SGX301
treatment in the first cycle was safe and well tolerated.
During
April 2020, analysis of the second open-label treatment cycle (“Cycle 2”) was completed, showing that continued treatment
with SGX301 twice weekly for an additional 6 weeks (12 weeks total) increased the positive response rate to 40% (p<0.0001 compared
to placebo and p<0.0001 compared to 6-weeks treatment). After the subsequent additional 6-week treatment, the response rate
in patients receiving a total of 12 weeks treatment increased two and a half-fold. Treatment responses were assessed at Week 8
(after 6 weeks of treatment) and at Week 16 (after 12 weeks of treatment). A positive response was defined as an improvement of
at least 50% in the CAILS score for the three index lesions evaluated in both Cycles 1 and 2. The data continued to indicate that
SGX301 is safe and well tolerated.
During
October 2020, analysis of the optional third open-label treatment cycle (“Cycle 3”) was completed. Cycle 3 was focused
on safety and all patients could elect to receive SGX301 treatment of all their lesions for an additional 6 weeks or up to 18
weeks in total. Of note, 66% of patients elected to continue with this optional safety cycle of the study. Of the subset of patients
that received SGX301 throughout all three cycles of treatment (18 weeks), 49% of them demonstrated a treatment response (p=0.046
vs. patients completing 12 weeks of SGX301 treatment in Cycle 2; p<0.0001 vs. patients receiving placebo in Cycle 1). Moreover,
in a subset of patients evaluated in this cycle, it was demonstrated that SGX301 is not systemically available, consistent with
the general safety of this topical product observed to date. At the end of Cycle 3, SGX301 continued to be well tolerated despite
extended and increased use of the product to treat multiple lesions.
In
addition, continued analysis of results from the protocol mandated efficacy cycles (Cycles 1 and 2) of the study revealed that
12 weeks of treatment (Cycle 2) with SGX301 was equally effective on both patch (response 37%, p=0.0009) and plaque (response
42%, p<0.0001) lesions when compared to Cycle 1 placebo lesion responses, further demonstrating the unique benefits of the
more deeply penetrating visible light activation of hypericin.
During
January 2021, we announced that we signed an exclusive Supply, Distribution and Services Agreement with The Daavlin Distributing
Co. (“Daavlin”), securing long-term supply and distribution of a commercially ready light device, which is an
integral component of the regulatory and commercial strategy for SGX301 for the treatment of CTCL.
Pursuant
to the Agreement, Daavlin will exclusively manufacture the proprietary light device for use with SGX301 for the treatment of CTCL.
Upon approval of SGX301 by the FDA, we will promote SGX301 and the companion light device, and facilitate the direct purchase
of the device from Daavlin. Daavlin will exclusively distribute and sell the SGX301 light device to us, physicians and patients.
In
February 2021, we announced that the Hong Kong Registrar of Patents granted a patent for the application titled "Formulations
and Methods of Treatment of Skin Conditions" (No. 16102842.8), published on January 29, 2021 under Publication
No. 1214771 B. The granted claims are directed to the therapeutic use of synthetic hypericin in the treatment of CTCL, similar
to those granted in Europe in 2020. This new patent is the first granted in Hong Kong and expands on our comprehensive
patent estate, which includes protection on the composition of the purified synthetic hypericin, methods of synthesis and therapeutic
methods of use in both CTCL and psoriasis.
We
estimate the potential worldwide market for SGX301 is in excess of $250 million for all applications, including the treatment
of CTCL. This potential market information is a forward-looking statement, and investors are urged not to place undue reliance
on this statement. While we have determined this potential market size based on assumptions that we believe are reasonable, there
are a number of factors that could cause our expectations to change or not be realized.
5
Cutaneous
T-Cell Lymphoma
CTCL
is a class of non-Hodgkin’s lymphoma (“NHL”), a type of cancer of the white blood cells that are an integral
part of the immune system. Unlike most NHLs, which generally involve B-cell lymphocytes (involved in producing antibodies), CTCL
is caused by an expansion of malignant T-cell lymphocytes (involved in cell-mediated immunity) normally programmed to migrate
to the skin. These skin-trafficking malignant T-cells migrate to the skin, causing various lesions to appear that may change shape
as the disease progresses, typically beginning as a rash and eventually forming plaques and tumors. Mycosis fungoides (“MF”)
is the most common form of CTCL. It generally presents with skin involvement only, manifested as scaly, erythematous patches.
Advanced disease with diffuse lymph node and visceral organ involvement is usually associated with a poorer response rate to standard
therapies. A relatively uncommon sub-group of CTCL patients present with extensive skin involvement and circulating malignant
cerebriform T-cells, referred to as Sézary syndrome. These patients have substantially graver prognoses (expected five-year
survival rate of 24%), than those with MF (expected five-year survival rate of 88%).
CTCL
mortality is related to stage of disease, with median survival generally ranging from about 12 years in the early stages to only
2.5 years when the disease has advanced. There is currently no FDA-approved drug for front-line treatment of early stage CTCL.
Treatment of early-stage disease generally involves skin-directed therapies. One of the most common unapproved therapies used
for early-stage disease is oral 5 or 8-methoxypsoralen (“Psoralen”) given with ultraviolet A (“UVA”) light,
referred to as PUVA, which is approved for dermatological conditions such as disabling psoriasis not adequately responsive to
other forms of therapy, idiopathic vitiligo and skin manifestations of CTCL in persons who have not been responsive to other forms
of treatment. Psoralen is a mutagenic chemical that interferes with DNA causing mutations and other malignancies. Moreover, UVA
is a carcinogenic light source that when combined with the Psoralen, results in serious adverse effects including secondary skin
cancers; therefore, the FDA requires a Black Box warning for PUVA.
CTCL
constitutes a rare group of NHLs, occurring in about 4% of the approximate 500,000 individuals living with NHL. We estimate, based
upon review of historic published studies and reports and an interpolation of data on the incidence of CTCL, that it affects over
20,000 individuals in the U.S., with approximately 2,800 new cases seen annually.
Dusquetide
Dusquetide
(research name: SGX94) is an IDR that regulates the innate immune system to simultaneously reduce inflammation, eliminate infection
and enhance tissue healing.
Dusquetide
is based on a new class of short, synthetic peptides known as IDRs. It has a novel mechanism of action in that it modulates the
body’s reaction to both injury and infection and is both simultaneously anti-inflammatory and anti-infective. IDRs have
no direct antibiotic activity but modulate host responses, increasing survival after infections with a broad range of bacterial
Gram-negative and Gram-positive pathogens including both antibiotic sensitive and resistant strains, as well as accelerating resolution
of tissue damage following exposure to a variety of agents including bacterial pathogens, trauma and chemo- or radiation-therapy.
IDRs represent a novel approach to the control of infection and tissue damage via highly selective binding to an intracellular
adaptor protein, sequestosome-1, also known as p62, which has a pivotal function in signal transduction during activation and
control of the innate defense system. Preclinical data indicate that IDRs may be active in models of a wide range of therapeutic
indications including life-threatening bacterial infections as well as the severe side-effects of chemo- and radiation-therapy.
Additionally, due to selective binding to p62, dusquetide may have potential anti-tumor action.
Dusquetide
has demonstrated efficacy in numerous animal disease models including mucositis, colitis, skin infection and other bacterial infections
and has been evaluated in a double-blind, placebo-controlled Phase 1 clinical trial in 84 healthy volunteers with both single
ascending dose and multiple ascending dose components. Dusquetide was shown to have a good safety profile and be well-tolerated
in all dose groups when administered by IV over 7 days and was consistent with safety results seen in pre-clinical studies. We
believe that market opportunities for dusquetide include, but are not limited to, oral and GI mucositis, acute Gram-positive bacterial
infections (e.g., methicillin resistant Staphylococcus aureus (MRSA)), acute Gram-negative infections (e.g., acinetobacter,
melioidosis), and acute radiation syndrome.
6
SGX942
– for Treating Oral Mucositis in Head and Neck Cancer
SGX942
is our product candidate containing our IDR technology, dusquetide, targeting the treatment of oral mucositis in head and neck
cancer patients. Oral mucositis in this patient population is an area of unmet medical need where there are currently no approved
drug therapies. Accordingly, we received Fast Track designation for the treatment of oral mucositis as a result of radiation and/or
chemotherapy treatment in head and neck cancer patients from the FDA. In addition, dusquetide has been granted PIM designation
in the UK by the MHRA for the treatment of severe oral mucositis in head and neck cancer patients receiving chemoradiation therapy.
The U.S. Patent and Trademark Office and the European Patent Office granted us the patent titled “Novel Peptides and Analogs
for Use in the Treatment of Oral Mucositis” on August 16, 2016 and January 23, 2019, respectively. The newly issued patent
claims therapeutic use of dusquetide and related IDR analogs, and adds to composition of matter claims for dusquetide and related
analogs that have been granted in the U.S. and worldwide.
We
initiated a Phase 2 clinical study of SGX942 for the treatment of oral mucositis in head and neck cancer patients in December
of 2013. We completed enrollment in this trial in the second half of 2015, and in December 2015 released positive preliminary
results. In this Phase 2 proof-of-concept clinical study that enrolled 111 patients, SGX942, at a dose of 1.5 mg/kg, successfully
reduced the median duration of severe oral mucositis by 50%, from 18 days to 9 days (p=0.099) in all patients and by 67%, from
30 days to 10 days (p=0.040) in patients receiving the most aggressive chemoradiation therapy for treatment of their head and
neck cancer. The p-values met the prospectively defined statistical threshold of p<0.1 in the study protocol. A less severe
occurrence of oral mucositis, ulcerative oral mucositis (defined as oral mucositis with a WHO score ≥2 corresponding to the
occurrence of overt ulceration in the mouth), was also monitored during the study. In the patients receiving the most aggressive
chemoradiation therapy, the median duration of oral mucositis was found to decrease from 65 days in the placebo treated patients
to 51 days in the patients treated with SGX942 1.5 mg/kg (p=0.099).
In
addition to identifying the best dose of 1.5 mg/kg, this study achieved all objectives, including increased incidence of “complete
response” of tumor at the one month follow-up visit (47% in placebo vs. 63% in SGX942 at 1.5 mg/kg). Decreases in mortality
and decreases in infection rate were also observed with SGX942 treatment, consistent with the preclinical results observed in
animal models.
SGX942
was found to be generally safe and well tolerated, consistent with the safety profile observed in the prior Phase 1 study conducted
in 84 healthy volunteers. The long-term (12 month) follow-up data was consistent with the preliminary positive safety and efficacy
findings. While the placebo population experienced the expected 12-month survival rate of approximately 80%, as defined in the
Surveillance, Epidemiology, and End Results statistics 1975-2012 from the National Cancer Institute, the SGX942 1.5 mg/kg treatment
group reported a 12-month survival rate of 93% (7% mortality in the SGX942 1.5 mg/kg group compared to 19% in the placebo group).
Similarly, tumor resolution (complete response) at 12 months was better in the SGX942 1.5 mg/kg treatment group relative to the
placebo population (80% in the 1.5 mg/kg group compared to 74% in the placebo group). Moreover, in the patients receiving chemotherapy
every third week, the SGX942 1.5 mg/kg treatment group had a tumor resolution rate (complete response) of 82% throughout the 12
months following chemoradiation therapy, while the placebo group experienced a 64% complete response rate. The long-term follow-up
results from the Phase 2 study are reviewed in “Dusquetide: Reduction in Oral Mucositis associated with Enduring Ancillary
Benefits in Tumor Resolution and Decreased Mortality in Head and Neck Cancer Patients” published online in Biotechnology
Reports and available at the following link: https://doi.org/10.1016/j.btre.2017.05.002. In addition to safety, evaluations of
other secondary efficacy endpoints, such as the utilization of opioid pain medication, indicated that the SGX942 1.5 mg/kg treatment
group had a 40% decrease in the use of opioids at the later stage of the treatment phase of the trial, when oral mucositis is
usually most severe and expected to increase pain medication use. This was in contrast to the placebo group, which demonstrated
a 10% increase in use of opioids over this same period. Data from this Phase 2 trial was published online in the Journal of Biotechnology.
The publication also delineates the supportive nonclinical data in this indication, demonstrating consistency in the qualitative
and quantitative biological response, including dose response, across the nonclinical and clinical data sets. The results are
available at the following link: http://authors.elservier.com/sd/article/S01681656116315668.
On
September 9, 2016, we and SciClone Pharmaceuticals, Inc. (“SciClone”) entered into an exclusive license agreement,
pursuant to which we granted rights to SciClone to develop, promote, market, distribute and sell SGX942 in defined territories.
Under the terms of the license agreement, SciClone will be responsible for all aspects of development, product registration and
commercialization in the territories, having access to data generated by us. In exchange for exclusive rights, SciClone will pay
us royalties on net sales, and we will supply commercial drug product to SciClone on a cost-plus basis, while maintaining worldwide
manufacturing rights.
7
During
July 2017, we initiated our pivotal Phase 3 clinical trial referred to as the “DOM–INNATE” study (Dusquetide
treatment in Oral Mucositis – by modulating INNATE immunity) with a controlled roll-out of U.S. study
sites, followed by the addition of European centers in 2018. Approximately 50 U.S. and European oncology centers are participating
in this pivotal Phase 3 study. Based on the positive and previously published Phase 2 results (Study IDR-OM-01), the pivotal Phase
3 clinical trial (Study IDR-OM-02) was a highly powered, double-blind, randomized, placebo-controlled, multinational trial that
sought to enroll approximately 260 subjects with squamous cell carcinoma of the oral cavity and oropharynx who were scheduled
to receive a minimum total cumulative radiation dose of 55 Gy fractionated as 2.0-2.2 Gy per day with concomitant cisplatin chemotherapy
given as a dose of 80-100 mg/m2 every third week. Subjects were randomized to receive either 1.5 mg/kg SGX942 or placebo
given twice a week during and for two weeks following completion of chemoradiation therapy (“CRT”). The primary endpoint
for the study was the median duration of SOM, which was assessed by oral examination at each treatment visit and then through
six weeks following completion of CRT. Oral mucositis is evaluated using the WHO Grading system. SOM is defined as a WHO Grade
of ≥3. Subjects are followed for an additional 12 months after the completion of treatment.
During September 2017, the National Institute of Dental and
Craniofacial Research (“NIDCR”), part of the NIH, awarded us a SBIR grant of approximately $1.5 million over two years
to support the conduct of our Phase 3, multinational, randomized, double-blind, placebo-controlled study evaluating SGX942 (dusquetide)
as a treatment for severe oral mucositis in patients with head and neck cancer receiving CRT. This grant was completed in August
2019.
On
April 9, 2019, the U.S. Patent Office issued a new patent No. 10,253,068 titled “Novel Peptides for Treating and Preventing
Immune-Related Disorders, Including Treating and Preventing Infection by Modulating Innate Immunity” for our dusquetide
related analogs.
In
April 2019, the Paediatric Committee of the EMA approved our Paediatric Investigation Plan (“PIP”) for SGX942, a prerequisite
for filing a Marketing Authorization Application (“MAA”) for any new medicinal product in Europe. The EMA also agreed
that we may defer conducting the PIP until successful completion of our ongoing pivotal Phase 3 clinical trial of SGX942, which
allows us to file the adult indication MAA prior to completion of the PIP.
In
August 2019, the NIDCR awarded us a Phase I SBIR grant of approximately $150,000 to support the evaluation of SGX942 (dusquetide)
in pediatric indications. This award will facilitate the assessment of SGX942 safety in juvenile animals, supporting future studies
in pediatric populations, including oral mucositis indications in pediatric patients undergoing stem cell transplants and treatments
for head and neck cancer.
During
August 2019, an independent DMC completed an unblinded interim analysis with data from approximately 90 subjects, including an
assessment of the Phase 3 DOM-INNATE study’s primary efficacy endpoint. The DMC provided a positive recommendation to randomize
approximately 70 additional subjects into the trial to maintain the rigorous assumption of 90% statistical power for the primary
efficacy endpoint. No safety concerns were reported by the DMC based on the interim analysis.
In
February 2020, the Japanese Patent Office granted the patent titled “Novel Peptides and Analogs for Use in the Treatment
of Oral Mucositis.” This allowance builds on similar intellectual property in the U.S., New Zealand, Australia and Singapore
and patent applications pending in other jurisdictions worldwide. The new claims cover therapeutic use of dusquetide (active ingredient
in SGX942) and related IDR analogs, and add to composition of matter claims for dusquetide and related analogs that have been
granted in the U.S. and worldwide.
8
In
June 2020, the pivotal Phase 3 DOM–INNATE study (Study IDR-OM-02) completed enrollment of 268 subjects. In December 2020,
we announced the results of our Phase 3 clinical trial for SGX942 noting that the primary endpoint of median duration of SOM did
not achieve the pre-specified criterion for statistical significance (p≤0.05); although biological activity was observed with
a 56% reduction in the median duration of SOM from 18 days in the placebo group to 8 days in the SGX942 treatment group. Despite
this clinically meaningful improvement, the variability in the distribution of the data yielded a p-value that was not statistically
significant. Other secondary endpoints supported the biological activity of dusquetide, including a statistically significant
50% reduction in the median duration of SOM in the per-protocol population, which decreased from 18 days in the placebo group
to 9 days in the SGX942 treatment group (p=0.049), consistent with the findings in the Phase 2 trial (Study IDR-OM-01). Similarly,
incidence of SOM also followed this biological trend as seen in the Phase 2 study, decreasing by 16% in the SGX942 treatment group
relative to the placebo group in the per-protocol population. The per-protocol population was defined as the population receiving
a minimum of 55 Gy radiation and at least 10 doses of study drug (placebo or SGX942) throughout the intended treatment period,
with no major protocol deviations (e.g. breaks in study drug administration longer than 8 days between successive doses). We are
analyzing the data to better determine why the study did not meet expectations. If there is any clarity gained from further analysis
of the dataset, especially with respect to specific subsets of patients that may benefit from SGX942 therapy, we will communicate
our findings and explore follow-up discussions with the FDA and the EMA.
Oral
Mucositis
Mucositis
is the clinical term for damage done to the mucosa by anticancer therapies. It can occur in any mucosal region, but is most commonly
associated with the mouth, followed by the small intestine. We estimate, based upon our review of historic studies and reports,
and an interpolation of data on the incidence of mucositis, that mucositis affects approximately 500,000 people in the U.S. per
year and occurs in 40% of patients receiving chemotherapy. Mucositis can be severely debilitating and can lead to infection, sepsis,
the need for parenteral nutrition and narcotic analgesia. The GI damage causes severe diarrhea. These symptoms can limit the doses
and duration of cancer treatment, leading to sub-optimal treatment outcomes.
The
mechanisms of mucositis have been extensively studied and have been linked to the interaction of chemotherapy and/or radiation
therapy with the innate defense system. Bacterial infection of the ulcerative lesions is regarded as a secondary consequence of
dysregulated local inflammation triggered by therapy-induced cell death, rather than as the primary cause of the lesions.
We
estimate, based upon our review of historic studies and reports, and an interpolation of data on the incidence of oral mucositis,
that oral mucositis is a subpopulation of approximately 90,000 patients in the U.S., with a comparable number in Europe. Oral
mucositis almost always occurs in patients with head and neck cancer treated with radiation therapy (greater than 80% incidence
of severe mucositis) and is common in patients undergoing high dose chemotherapy and hematopoietic cell transplantation, where
the incidence and severity of oral mucositis depends greatly on the nature of the conditioning regimen used for myeloablation.
Oral
BDP
Oral
BDP (beclomethasone 17,21-dipropionate) represents a first-of-its-kind oral, locally acting therapy tailored
to treat GI inflammation. BDP has been marketed in the U.S. and worldwide since the early 1970s as the active pharmaceutical ingredient
in a nasal spray and in a metered-dose inhaler for the treatment of patients with allergic rhinitis and asthma. Oral BDP is specifically
formulated for oral administration as a single product consisting of two tablets. One tablet is intended to release BDP in the
upper sections of the GI tract and the other tablet is intended to release BDP in the lower sections of the GI tract.
Based
on its pharmacological characteristics, oral BDP may have utility in treating other conditions of the GI tract having an inflammatory
component. We are planning to pursue development programs for the treatment of pediatric Crohn’s disease, acute radiation
enteritis and GI acute radiation syndrome pending further grant funding. We are also exploring the possibility of testing oral
BDP for local inflammation associated with ulcerative colitis, among other indications.
In
July 2019, the European Patent Office issued two patents, both titled “Topically Active Steroids for use in Radiation and
Chemotherapeutic Injury”, following the expiration of the objection period. The new patents (#2,373,160 and #2,902,031)
claim use of oral beclomethasone 17,21-dipropionate (BDP) for treatment of damage to the GI tract as a result of acute radiation
injury, including total body irradiation in the accidental or biodefense context.
We
estimate the potential worldwide market for oral BDP is in excess of $500 million for all applications, including the treatment
of pediatric Crohn’s disease. This potential market information is a forward-looking statement, and investors are urged
not to place undue reliance on this statement. While we have determined this potential market size based on assumptions that we
believe are reasonable, there are a number of factors that could cause our expectations to change or not be realized.
9
SGX203
– for Treating Pediatric Crohn’s Disease
SGX203
is a two tablet delivery system of BDP specifically designed for oral use that allows for administration of immediate and delayed
release BDP throughout the small bowel and the colon. The FDA has given SGX203 Orphan Drug designation as well as Fast Track designation
for the treatment of pediatric Crohn’s disease. We will pursue a pivotal Phase 3 clinical trial of SGX203 for the treatment
of pediatric Crohn’s disease contingent upon additional funding, such as through partnership funding support.
Pediatric
Crohn’s Disease
Crohn’s
disease causes inflammation of the GI tract. Crohn’s disease can affect any area of the GI tract, from the mouth to the
anus, but it most commonly affects the lower part of the small intestine, called the ileum. The swelling caused by the disease
extends deep into the lining of the affected organ. The swelling can induce pain and can make the intestines empty frequently,
resulting in diarrhea. Because the symptoms of Crohn’s disease are similar to other intestinal disorders, such as irritable
bowel syndrome and ulcerative colitis, it can be difficult to diagnose. People of Ashkenazi Jewish heritage have an increased
risk of developing Crohn’s disease.
Crohn’s
disease can appear at any age, but it is most often diagnosed in adults in their 20s and 30s. However, approximately 30% of people
with Crohn’s disease develop symptoms before 20 years of age. We estimate, based upon our review of historic published studies
and reports, and an interpolation of data on the incidence of pediatric Crohn’s disease, that pediatric Crohn’s disease
is a subpopulation of approximately 80,000 patients in the U.S. with a comparable number in Europe. Crohn’s disease tends
to be both severe and extensive in the pediatric population and a relatively high proportion (approximately 40%) of pediatric
Crohn’s patients have involvement of their upper GI tract.
Crohn’s
disease presents special challenges for children and teens. In addition to bothersome and often painful symptoms, the disease
can stunt growth, delay puberty, and weaken bones. Crohn’s disease symptoms may sometimes prevent a child from participating
in enjoyable activities. The emotional and psychological issues of living with a chronic disease can be especially difficult for
young people.
SGX201
– for Preventing Acute Radiation Enteritis
SGX201
is a delayed-release formulation of BDP specifically designed for oral use. In 2012, we completed a Phase 1/2 clinical trial testing
SGX201 in prevention of acute radiation enteritis. Patients with rectal cancer scheduled to undergo concurrent radiation and chemotherapy
prior to surgery were randomized to one of four dose groups. The objectives of the study were to evaluate the safety and maximal
tolerated dose of escalating doses of SGX201, as well as the preliminary efficacy of SGX201 for prevention of signs and symptoms
of acute radiation enteritis. The study demonstrated that oral administration of SGX201 was safe and well tolerated across all
four dose groups. There was also evidence of a potential dose response with respect to diarrhea, nausea and vomiting and the assessment
of enteritis according to National Cancer Institute Common Terminology Criteria for Adverse Events for selected GI events. In
addition, the incidence of diarrhea was lower than that seen in published historical control data in this patient population.
This program was supported in part by a $500,000 two-year SBIR grant awarded by the NIH. We continue to work with our Radiation
Enteritis medical advisors to identify additional funding opportunities to support the clinical development program.
We
have received Fast Track designation from the FDA for SGX201 for acute radiation enteritis.
10
Acute
Radiation Enteritis
External
radiation therapy is used to treat most types of cancer, including cancer of the bladder, uterine, cervix, rectum, prostate, and
vagina. During delivery of treatment, some level of radiation will also be delivered to healthy tissue, including the bowel, leading
to acute and chronic toxicities. The large and small bowels are very sensitive to radiation and the larger the dose of radiation
the greater the damage to normal bowel tissue. Radiation enteritis is a condition in which the lining of the bowel becomes swollen
and inflamed during or after radiation therapy to the abdomen, pelvis, or rectum. Most tumors in the abdomen and pelvis need large
doses, and almost all patients receiving radiation to the abdomen, pelvis, or rectum will show signs of acute enteritis.
Patients
with acute enteritis may have nausea, vomiting, abdominal pain and bleeding, among other symptoms. Some patients may develop dehydration
and require hospitalization. With diarrhea, the GI tract does not function normally, and nutrients such as fat, lactose, bile
salts, and vitamin B12 are not well absorbed.
Symptoms
will usually resolve within two to six weeks after therapy has ceased. Radiation enteritis is often not a self-limited illness,
as over 80% of patients who receive abdominal radiation therapy complain of a persistent change in bowel habits. Moreover, acute
radiation injury increases the risk of development of chronic radiation enteropathy, and overall 5% to 15% of the patients who
receive abdominal or pelvic irradiation will develop chronic radiation enteritis.
We
estimate, based upon our review of historic published studies and reports, and an interpolation of data on the treatment courses
and incidence of cancers occurring in the abdominal and pelvic regions, there to be over 100,000 patients annually in the U.S.,
with a comparable number in Europe, who receive abdominal or pelvic external beam radiation treatment for cancer, and these patients
are at risk of developing acute and chronic radiation enteritis.
Public
Health Solutions Overview
ThermoVax®
– Thermostability Technology
ThermoVax®
is a novel method for thermostabilizing vaccines with a variety of adjuvants, resulting in a single vial which can be reconstituted
with water for injection immediately prior to use.