Item 1A. Risk Factors 28
Item 1B. Unresolved Staff Comments 50
Item 2. Properties. 50
Item 3. Legal Proceedings. 50
Item 4. Mine Safety Disclosures. 50
Part II
Item 6. Selected Financial Data 52
Item 7A. Quantitative and Qualitative Disclosures About Market Risk. 61
Item 8. Financial Statements and Supplementary Data 61
Item 9. Changes in and Disagreements with Accountants 62
Item 9A. Controls and Procedures 62
Item 9B. Other Information 63
Part III
Item 10. Directors, Executive Officers and Key Employees 63
Item 11. Executive Compensation 63
Item 14. Principal Accounting Fees and Services 64
Part IV
Item 15. Exhibits, Financial Statement Schedules 64
GLOSSARY
OF CERTAIN SCIENTIFIC TERMS
The
medical and scientific terms used in this Annual Report on Form 10-K have the following meanings:
“Active
metabolite” means a drug that is processed by the body into an altered form which effects the body.
“Agonist”
means a chemical/drug that binds to a receptor in the body and activates that receptor to produce a biological response.
“Analog”
means a compound having a structure similar to that of an approved drug but differing from it with respect to a certain component
of the molecule which may cause it to have similar or different effects on the body.
“cGCP”
means current Good Clinical Practices. The FDA and other regulatory agencies promulgate regulations and standards, commonly referred
to as current Good Clinical Practices, for designing, conducting, monitoring, auditing and reporting the results of clinical trials
to ensure that the data and results are accurate and that the rights and welfare of trial participants are adequately protected.
“cGMP”
means current Good Manufacturing Practices. The FDA and other regulatory agencies promulgate regulations and standards, commonly
referred to as current Good Manufacturing Practices, which include requirements relating to quality control and quality assurance,
as well as the corresponding maintenance of records and documentation.
“CRO”
means Contract Research Organization.
“Deuterated
analog” means a small molecule in which one or more of the hydrogen atoms are replaced by deuterium.
“EMA”
means the European Medicines Agency.
“FDA”
means the Food and Drug Administration.
“IND”
means an Investigational New Drug Application. Before testing a new drug on human subjects, the company must file an IND with
the FDA. Information must be produced on the absorption, distribution, metabolism, and excretion properties of the drug and detailed
protocols for testing on human subjects must be submitted.
“Indication”
means a condition which makes a particular treatment or procedure advisable.
“Moiety”
means an active or functional part of a molecule.
“NDA”
means a New Drug Application submitted to the FDA. Under the Food, Drug, and Cosmetic Act of 1938, an NDA is submitted to the
FDA enumerating the uses of the drug and providing evidence of its safety.
“NL”
means Necrobiosis Lipoidica, a rare chronic, and granulomatous disorder.
“Osteonecrosis”
means the death of bone cells due to decreased blood flow. It can lead to pain and collapse of areas of bone.
SPECIAL
NOTE REGARDING FORWARD-LOOKING STATEMENTS AND RISK FACTOR SUMMARY
This
Annual Report on Form 10-K contains forward-looking statements that involve risks and uncertainties. All statements other than
statements of historical facts contained in this Form 10-K are forward-looking statements. In some cases, you can identify forward-looking
statements by words such as “anticipate,” “believe,” “contemplate,” “continue,”
“could,” “estimate,” “expect,” “intend,” “may,” “plan,”
“potential,” “predict,” “project,” “seek,” “should,” “target,”
“will,” “would,” or the negative of these words or other comparable terminology. We have based these forward-looking
statements on our current expectations and projections about future events and trends that we believe may affect our financial
condition, results of operations, strategy, short- and long-term business operations and objectives, and financial needs. These
forward-looking statements are subject to a number of risks, uncertainties and assumptions, including those described in “Risk
Factors” and elsewhere in this Form 10-K. Moreover, we operate in a very competitive and rapidly changing environment, and
new risks emerge from time to time. It is not possible for our management to predict all risks, nor can we assess the impact of
all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially
from those contained in any forward-looking statements we may make. In light of these risks, uncertainties and assumptions, the
forward-looking events and circumstances discussed in this Form 10-K may not occur, and actual results could differ materially
and adversely from those anticipated or implied in the forward-looking statements. Given these uncertainties, you should not place
undue reliance on these forward-looking statements. These risks are discussed more fully in the “Risk Factors” section
of this Annual Report on Form 10-K. These risks include, but are not limited to, the following:
● our ability to obtain funding for our future operations;
● our ability to recruit and enroll suitable patients in our clinical trials;
● the pricing and reimbursement of our product candidates, if approved;
● developments relating to our competitors and our industry;
● our financial performance.
You
should not rely upon forward-looking statements as predictions of future events. Although we believe that the expectations reflected
in the forward-looking statements are reasonable as of the date of this Form 10-K, we cannot guarantee that the future results,
levels of activity, performance or events and circumstances reflected in the forward-looking statements will be achieved or occur.
We undertake no obligation to update publicly any forward-looking statements for any reason after the date of this Form 10-K to
conform these statements to new information, actual results or to changes in our expectations, except as required by law.
You
should read this Form 10-K and the documents that we reference in this Form 10-K and have filed with the SEC as exhibits with
the understanding that our actual future results, levels of activity, performance, and events and circumstances may be materially
different from what we expect.
In
this Form 10-K, “we,” “us”, “our”, “Processa” and “the Company” refer
to Processa Pharmaceuticals, Inc. and its subsidiary.
Part
I
Item
1. Business
Overview
Our
mission is to develop drug products that improve the survival and/or quality of life for patients with high unmet medical need
conditions. We are a development company, not a discovery company, that seeks to identify and develop drugs for patients who need
better treatment options than presently exist for their medical condition. In order to increase the probability of development
success, our pipeline only includes drugs which have previously demonstrated some efficacy in the targeted population or a drug
with very similar pharmacological properties has been shown to be effective in the population.
We are a clinical-stage
biopharmaceutical company focused on the development of drug products that are intended to provide treatment for patients who
have a high unmet medical need condition that effects survival or the patient’s quality of life and have few or no treatment
options. We currently have three drugs in various stages of clinical development. Our most advanced product candidate, PCS499,
is an oral tablet that is a deuterated analog of one of the major metabolites of pentoxifylline (PTX or Trental®). We have
completed a Phase 2A trial for PCS499 and will begin recruiting for a Phase 2 trial in the first half of 2021. In 2020, we in-licensed
PCS6422 (eniluracil) from Elion Oncology and PCS12852 from Yuhan Corporation. PCS6422 will be orally administered in combination
with capecitabine in a Phase 1B dose-escalation study in patients with Advanced Refractory Gastrointestinal (GI) Tract Tumors,
with recruitment beginning in the first half of 2021. PCS12852 has already been evaluated in clinical studies in South Korea and
we anticipate a response back to our pre-IND meeting questions by March 31, 2021. Our remaining two drug assets whose active molecules
have been shown to be clinically efficacious require additional toxicology data in order to advance these candidates
to an IND stage of development.
Our
Strategy
Our strategy is to
acquire or in-license development candidates that will not only treat a specific group of patients with unmet medical needs, but
may also have the potential to chart a more efficient path to registration. In many instances, these clinical candidates have
significant pre-clinical and clinical data that we can leverage to high value inflection points while de-risking the programs
and adding in optionality to potential future indications. The regulatory science approach our team has developed over the last
20+ years seeks to leverage the earlier data and identify the least risk path toward commercialization/registration of these drugs.
We apply rigorous standards to identify drugs for our portfolio, namely:
Our
Team
Our
drug development efforts are guided by our knowledge and experience in applying rigorous regulatory science to decrease manageable
risks, costs and time toward achieving marketing authorization from regulatory authorities including the FDA. We have assembled
a seasoned management team and development team with extensive experience in developing therapies, including advancing product
candidates from preclinical research through clinical development and ultimately regulatory approval and commercialization. Over
their careers, our team has successfully obtained over 30 FDA approvals across all divisions of the FDA. Our team is led by our
Chairman and CEO David Young, Pharm.D., Ph.D. who has extensive experience in research, regulatory approval and business development
and who served at Questcor for eight years, initially as an independent director and subsequently as its Chief Scientific Officer.
Dr. Young’s guidance led to the approval of Acthar in Infantile Spasms and the ultimate sale of Questcor in 2014.
Our
Pipeline
The
table below summarizes our clinical product pipeline. We completed our Phase 2A clinical trial for PCS499 in December 2020.
A
summary of each drug is presented below organized by phase of development. It should be noted, however, that we expect the Phase
2 PCS499 and Phase 1B PCS6422 studies to have their first patient enrolled in the first half of 2021 with interim data obtained
in the second half of 2021. The PCS12852 Phase 2A study will likely have first patient enrolled at end of 2021 or beginning of
2022, depending on discussions with the FDA.
PCS499
Our
most advanced product candidate, PCS499, is an oral tablet that is a deuterated analog of one of the major metabolites
of pentoxifylline (PTX or Trental®). PCS499 is classified by FDA as a new molecular entity. PCS499 and its metabolites
act on multiple pharmacological targets that are important in a variety of conditions. We have targeted Necrobiosis Lipoidica
(NL) as our lead indication for PCS499. NL is a chronic, disfiguring condition affecting the skin and tissue under the skin typically
on the lower extremities with no currently approved FDA treatments. NL presents more commonly in women than in men and occurs
more often in people with diabetes. Ulceration occurs in approximately 30% of NL patients, which can lead to more severe complications,
such as deep tissue infections and osteonecrosis threatening the life of the limb. Approximately 22,000 - 55,000 people in the
United States and more than 120,000 people outside the United States are affected with ulcerated NL.
The
degeneration of tissue occurring at the NL lesion site may be caused by a number of pathophysiological changes, which make it
extremely difficult to develop effective treatments for this condition. Because PCS499 and its metabolites appear to affect most
of the biological pathways that contribute to the pathophysiology associated with NL, PCS499 may provide a novel treatment solution
for NL.
On
June 18, 2018, the FDA granted orphan-drug designation for PCS499 for the treatment of NL. On September 28, 2018, the IND for
PCS499 in NL became effective, such that we initiated and completed a Phase 2A multicenter, open-label prospective trial
designed to determine the safety and tolerability of PCS499 in patients with NL. The study initially had a six-month
treatment phase and a six-month optional extension phase. In December 2019, we informed patients and sites that the study
would conclude after the treatment phase and there would no longer be an extension phase. The first enrolled NL patient in
this Phase 2A clinical trial was dosed on January 29, 2019 and the study completed enrollment on August 23, 2019. The last
patient visit took place in February 2020. Due to COVID-19 related restrictions at certain sites, study closeout, database
lock and final report were delayed and have only recently been completed.
The
primary objective of the trial was to evaluate the safety and tolerability of PCS499 in patients with NL and to use the safety
and efficacy data to design future clinical trials. Based on toxicology studies and healthy human volunteer studies, Processa
and the FDA agreed that a PCS499 dose of 1.8 grams/day would be the highest dose administered to NL patients in this Phase 2A
trial. As anticipated, the PCS499 dose of 1.8 grams/day, 50% greater than the maximum tolerated dose of PTX, appeared to be well
tolerated with no serious adverse events (SAEs) reported. All adverse events (AEs) reported in the study were mild in severity.
As expected, gastrointestinal symptoms were the most frequent adverse events and reported in four patients, all of which resolved
within 1-2 weeks of starting dosing.
Two
of the twelve patients in the study presented with more severe ulcerated NL and had ulcers for more than two months prior to dosing.
At baseline, the reference ulcer in one of the two patients measured 3.5 cm2 and had completely closed by Month 2 of
treatment. The second patient had a baseline reference ulcer of 1.2 cm2 which completely closed by Month 9 during the
patient’s treatment extension period. In addition, while in the trial, both patients also developed small ulcers at other
sites, possibly related to contact trauma, and these ulcers resolved within one month. However, the other ten patients, presenting
with mild to moderate NL and no ulceration, had more limited improvement of the NL lesions during treatment. Historically, 13
- 20% of all the patients with NL naturally progress to complete healing over many years after presenting with NL. Although the
natural healing of the more severe ulcerated NL patients has not been evaluated independently, medical experts who treat NL patients
suggest that the natural progression of an open ulcerated wound to complete closure would be significantly less than 13% over
1-2 years and probably close to 0% in patients with the larger ulcers.
On
March 25, 2020, we met with the FDA and discussed the clinical program, as well as the nonclinical and clinical pharmacology plans
to ultimately support the submission of the PCS499 New Drug Application (NDA) in the U.S. for the treatment of ulcers in NL patients.
With input from the FDA, we have designed the next trial as a randomized, placebo-controlled Phase 2 study to evaluate the ability
of PCS499 to completely close ulcers in patients with NL and better understand the potential response of NL patients on drug and
on placebo. We will begin recruiting for the randomized, placebo-controlled trial in the first half of 2021. After obtaining the
results from this Phase 2 study, we expect to meet with the FDA at an end of Phase 2 meeting to agree on the design of the Phase
3 study, to define a Special Protocol Assessment for the Phase 3 study and to agree on the next steps to obtain approval.
PCS12852
On
August 19, 2020, we in-licensed PCS12852 (formerly known as YH12852) from Yuhan Corporation (“Yuhan”), pursuant to
which we acquired an exclusive license to develop, manufacture and commercialize PCS12852 globally, excluding South Korea.
PCS12852
is a novel, potent and highly selective 5-hydroxytryptamine 4 (5-HT4) receptor agonist. Other 5-HT receptor agonists with less
5-HT4 selectivity have been shown to successfully treat gastrointestinal (GI) motility disorders such as gastroparesis, chronic
constipation, constipation-predominant irritable bowel syndrome, and functional dyspepsia. Less selective 5-HT4 agonists, such
as cisapride, have been either removed from the market or not approved because of the cardiovascular side effects associated with
the drugs binding to other receptors, especially receptors other than 5-HT4.
We plan to obtain guidance
from the FDA in the first half of 2021 to further define the clinical development program required for the PCS12852 product and
a Phase 2A proof-of-concept randomized, placebo-controlled study for PCS12852 in patients with gastroparesis. The purpose of the
Phase 2A trial is to define a dosing regimen of PCS12852 to demonstrate efficacy and safety in a larger
pivotal study. Since patients with gastroparesis have an abnormal pattern of upper GI motility in the absence of mechanical obstruction,
the Phase 2A study will be designed to evaluate the change on gastric emptying in patients with gastroparesis on two different
dosing regimens of PCS12852 compared to placebo. The only FDA-approved drug to treat gastroparesis is metoclopramide, a
dopamine D2 receptor antagonist that has serious side effects and can only be used as a short-term treatment. Other 5-HT4 drugs
have been used clinically but the side effects, caused mainly by binding to other receptors, has resulted in these drugs not being
a viable option to treat patients with gastroparesis. It should be noted that PCS12852 is a highly specific 5-HT4 agonist that
has been shown in non-clinical studies to have a cardiovascular side effect only at concentrations greater than 1,000 times the
maximum concentration seen in humans.
Two
clinical studies, both which have demonstrated the effectiveness of PCS12852 on GI motility, have been previously conducted by
Yuhan with PCS12852. In a Phase 1 trial (Protocol YH12852-101), the initial safety and tolerability of PCS12852 were evaluated
after single and multiple oral doses in healthy subjects. PCS12852 was shown to increase GI motility in this study, increasing
stool frequency with faster onset when compared to prucalopride, an FDA-approved drug for the treatment of chronic idiopathic
constipation. Based on an increase of ≥1 spontaneous bowel movement (SBM)/week from baseline during 7-day multiple dosing,
the PCS12852 dose group had a higher percent of patients with an increase than the prucalopride group. All doses of PCS12852 were
safe and well tolerated and no SAEs occurred during the study. The most frequently reported AEs were headache, nausea and diarrhea
which were temporal, manageable, and reversible within 24 hours. There were no clinically significant changes in platelet aggregation
and ECG parameters including a change in QTc prolongation in the study. In a Phase 1/2A clinical trial (Protocol YH12852-102),
the safety, tolerability, gastric emptying rate and pharmacokinetics of multiple doses of a PCS12852 immediate release (IR) formulation
and a delayed release (DR) formulation were evaluated. PCS12852 was safe and well tolerated after single and multiple administrations.
The most frequent AEs for both the IR and DR formulations of PCS12852 were headache, nausea and diarrhea, but the incidences of
these AEs were comparable with those of the 2mg prucalopride (a 5-HT4 agonist) group. These AEs, which were transient and mostly
mild in severity, are also commonly observed with other 5-HT4 agonists. Both formulations of PCS12852 also increased the gastric
emptying rate and increased GI motility.
Yuhan
had also conducted extensive toxicological studies for the product that demonstrated that the product is safe for use and can
be moved into Phase 2 studies.
PCS6422
On
August 23, 2020, we in-licensed PCS6422 from Elion Oncology, Inc. (“Elion”), pursuant to which we acquired an exclusive
license to develop, manufacture and commercialize PCS6422 globally.
Elion acquired
eniluracil (PCS6422) from Fennec Pharmaceuticals (formerly known as Adherex Technologies) in 2016. PCS6422 is an oral,
potent, selective and irreversible inhibitor of dihydropyrimidine dehydrogenase (DPD), the enzyme that rapidly metabolizes a
common chemotherapy drug known as 5-FU, into inactive metabolites, such as α-fluoro-β-alanine (F-Bal). F-Bal is a
metabolite that has no anti-cancer activity but causes unwanted side effects, which notably leads to
dose interruptions and significantly affect a patient’s quality of life. F-Bal is thought to cause the
neurotoxicity and Hand–Foot Syndrome (HFS) associated with 5-FU, and greater formation of F-Bal appears to be
associated with a decrease in the antitumor activity of 5-FU. HFS can affect activities of daily living, quality of
life, and requires dose interruptions/adjustments and even therapy discontinuation resulting in suboptimal tumor effects. We
believe that the inhibition of DPD by PCS6422 may significantly improve exposure to 5-FU and reduce 5-FU side effects related
to F-Bal. One dose of PCS6422 irreversibly blocks DPD activity for up to two weeks until DPD levels recover via de novo
synthesis. Thus, we believe inhibition of tumor DPD will result in higher 5-FU intra-tumoral concentration and potentially
better tumor response (efficacy) along with the decrease in F-Bal (improved safety).
Fluoropyrimidines (e.g.,
5-FU) remain the cornerstone of treatment for many different types of cancers, either as monotherapy or in combination
with other chemotherapy agents by an estimated two million patients annually. Xeloda®, the brand name of capecitabane,
is an oral pro-drug of 5-FU and approved as first-line therapy for metastatic colorectal and breast cancer. However,
its use is limited by adverse effects such as the development of HFS in up to 60% of patients.
Elion
evaluated the potential for the combination of PCS6422 with capecitabine as a treatment of advanced gastrointestinal
(GI) tumors. Nonclinical efficacy data indicated that in colorectal cancer models, pretreatment with PCS6422 enhanced the antitumor
activity of capecitabine. PCS6422 dramatically increased the antitumor potency of capecitabine without increasing the toxicity.
The antitumor efficacy of the combination of PCS6422 and capecitabine was tested in several xenograft animal models with human
breast, pancreatic and colorectal cancer cells. These preclinical xenograft models demonstrate that PCS6422 potentiates the antitumor
activity of capecitabine and significantly reduces the dose of capecitabine required to be efficacious.
Elion
met with the FDA in 2019 and agreed upon the clinical development program required for the combination of PCS6422 and capecitabine
as first-line therapy for metastatic colorectal cancer when treatment with fluoropyrimidine therapy alone is preferred. On May
17, 2020, an IND for the Phase 1B study was granted safe to proceed by the FDA. This Phase 1B study will evaluate i) the safety
and tolerability of a fixed dose of PCS6422 and several doses of capecitabine in advanced GI tumor patients, ii) the pharmacokinetics
of PCS6422, capecitabine,
5-FU and selected metabolites, and iii) the activity of DPD over time after PCS6422 administration. The study will begin patient
recruitment in the first half of 2021.
Other
DPD enzyme inhibitors (e.g. Gimeracil used in Teysuno® approved only outside the US) act as competitive reversible inhibitors.
These agents must be present when 5-FU or capecitabine are administered to inhibit 5-FU breakdown by DPD in order to improve the
efficacy and safety profiles of 5-FU. Given the reversible nature of their effect on DPD, over time 5-FU metabolism to F-Bal will
return, decreasing the amount of 5-FU in the cancer cells and decreasing the potential cytotoxicity on the cancer cells. There
is also evidence that administering DPD inhibitors directly with 5-FU may also decrease the antitumor effect of the 5-FU. Because
PCS6422 is an irreversible inactivator of DPD, it can be dosed the day before capecitabine administration and its effect on DPD
can last longer than the reversible DPD inhibitors and beyond the time 5-FU exists in the cancer cell. We believe this can optimize
the potential cytotoxic effect and minimize the catabolism of 5-FU to F-Bal.
Prior
to Elion’s involvement, two multicenter Phase 3 studies were conducted in patients with colorectal cancer with PCS6422 administered
in 10-fold excess to 5-FU and administered with the 5-FU. Unfortunately, we believe the dose of PCS6422 during these trials was
not optimal and that PCS6422 was not administered early enough to irreversibly affect the DPD enzyme, thus the regimen tended
to produce less antitumor benefit than the control arm with the standard regimen of 5-FU/leucovorin (LV) without PCS6422. Later
preclinical work suggested that when PCS6422 was present at the same time as and in excess to 5-FU, it diminished the antitumor
activity of 5-FU, which we believe supports the proposal of exploring clinically dosing PCS6422 several hours before 5-FU to allow
its complete clearance before the administration of 5-FU.
PCS11T
On
May 24, 2020, we in-licensed PCS11T (formerly known as ATT-11T) from Aposense, Ltd. (“Aposense”), pursuant to which
we were granted Aposense’s patent rights and Know-How to develop and commercialize their next generation irinotecan cancer
drug, PCS11T.
PCS11T
is a novel lipophilic anti-cancer pro-drug that is being developed for the treatment of the same solid tumors as prescribed for
irinotecan. This pro-drug is a conjugate of a specific proprietary Aposense molecule connected to SN-38, the active metabolite
of irinotecan. The proprietary molecule in PCS11T has been designed to allow PCS11T to bind to cell membranes to form an inactive
pro-drug depot on the cell with SN-38 preferentially accumulating in the membrane of tumors cells and the tumor core. This unique
characteristic may make the therapeutic window of PCS11T wider than other irinotecan products such that the antitumor effect of
PCS11T could occur at a much lower dose with a milder adverse effect profile than irinotecan. Despite the widespread use of commercially
marketed irinotecan products in the treatment of metastatic colorectal cancer and other cancers resulting in peak annual sales
of approximately $1.1 billion, irinotecan has a narrow therapeutic window and includes an FDA “Black Box” warning
for both neutropenia and severe diarrhea. There is, therefore, a substantial unmet need to overcome the limitations of the current
commercially marketed irinotecan products, improving efficacy and reducing the severity of treatment emergent AEs. We believe
the potential wider therapeutic window of PCS11T will likely lead to more patients responding with less side effects when on PCS11T
compared to other irinotecan products.
Pre-clinical
studies conducted to date showed that PCS11T demonstrated tumor eradication at much lower doses than irinotecan across various
tumor xenograft models. PCS11T does not affect acetyl choline esterase (AChE) activity in human and rat plasma in vitro, which
would suggest that PCS11T will show an improved safety profile, compared to irinotecan, which is known for its cholinergic-related
side effects.
We
are currently planning to manufacture the product at a GMP facility, conduct the required toxicological studies required to file
the IND and initiate the Phase 1B study in oncology patients with solid tumors in 2022.
PCS100
On
August 29, 2019, we entered into an exclusive license agreement with Akashi Therapeutics, Inc. (“Akashi”) to develop
and commercialize an anti-fibrotic, anti-inflammatory drug, PCS100 (formerly known as HT-100), which also promotes healthy muscle
fiber regeneration. In previous clinical trials in Duchenne Muscular Dystrophy (DMD), PCS100 showed promising improvement in the
muscle strength of non-ambulant pediatric patients. Although the FDA placed a full clinical hold on the DMD trial after an SAE
in a pediatric patient, the FDA has partially removed the clinical hold and defined how PCS100 can resume clinical trials in DMD.
We are presently evaluating potential development programs.
Manufacturing
and Clinical Supplies
We
do not own or operate, and currently have no plans to establish, any manufacturing facilities. We currently rely, and expect to
continue to rely, on third party contract manufacturing organizations (CMOs), for the supply of cGMP-grade clinical trial materials
and commercial quantities of our product candidates and products, if approved. We require all of our CMOs to conduct manufacturing
activities in compliance with cGMP. We have assembled a team of experienced employees and consultants to provide the necessary
technical, quality and regulatory oversight of our CMOs.
We
anticipate that these CMOs will have the capacity to support both clinical supply and commercial-scale production, but we do not
have any formal agreements at this time with any of these CMOs to cover commercial production.
We
also may elect to pursue additional CMOs for manufacturing supplies of drug substance and finished drug product in the future.
We believe that our standardized manufacturing process can be transferred to a number of other CMOs for the production of clinical
and commercial supplies of our product candidates in the ordinary course of business.
Competition
Many
of our potential competitors may have significantly greater financial resources, a more established presence in the market, and
more expertise in research and development, manufacturing, pre-clinical and clinical testing, obtaining regulatory approvals and
reimbursement, and marketing approved products than we do. Mergers and acquisitions in the pharmaceutical, biotechnology and diagnostic
industries may result in even more resources being concentrated among a smaller number of our competitors. Smaller or early-stage
companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established
companies. These potential competitors may also compete with us in recruiting and retaining top qualified scientific, sales, marketing
and management personnel and establishing clinical trial sites and patient registration for clinical trials, as well as in acquiring
technologies complementary to, or necessary for, our programs.
The
key competitive factors affecting each of our products, if approved, are likely to include the efficacy, safety, convenience and
price of the products relative to other approved products used on-label or off-label for each unmet medical need condition. Although
preliminary clinical data exists to support the possibility of improved efficacy and safety profiles for our drugs, more in-depth
randomized, controlled studies are required for our products to determine if our preliminary findings will support the approval
in the designated unmet medical need indication.
For
PCS499, there are currently no FDA-approved drugs for the treatment of patients with NL, and few drugs are used off-label for
NL given the lack of efficacy and/or side effect concerns.
For
PCS12852, the competitive factors will include establishing marketing penetration against the metoclopramide products (the only
approved drug gastroparesis) and other 5-HT4 receptor agonists used off label. The market penetration will depend on the potential
for an improved safety profile due to the very selective 5-HT4 receptor binding by PCS12852 and similar or greater efficacy in
the treatment of gastroparesis.
For
PCS6422, the competitive factors will be related to the efficacy and safety of the product when used in combination with existing
cytotoxic drugs such as capecitabine and fluoropyrimidines compared to the efficacy and safety when these cytotoxic agents are
administered without PCS6422 or with reversible enzyme inhibitors. The market penetration will depend on how much improvement
will occur in the efficacy and/or safety profiles when administered in combination with PCS6422. Currently, there are no other
reversible or irreversible enzyme inhibitor products approved in the US and no irreversible enzyme inhibitors approved ex-US,
which may make PCS6422 the first DPD irreversible inhibitor available in the US and ex-US.
For
PCS11T, the competitive factors will include establishing marketing penetration against the existing irinotecan product (Camptosar®)
and the newer liposomal irinotecan product (Onivyde®). The establishment of that market will be based upon improved efficacy
and/or safety of PCS11T.
For
PCS100, the competitive factors will be contingent on the indication chosen for the product. For the adult fibrotic conditions
currently being evaluated, very few treatment options are currently approved and are usually limited in efficacy and/or safety.
For the DMD indication, the existing therapies are either limited for use in patients with specific genetic mutations or may show
initial improvements in the treatment of DMD, but the improvement diminishes over time and, therefore, new treatments are still
needed.
Our
commercial opportunity for any of our product candidates could be reduced or eliminated if our competitors develop and commercialize
products that are safer, more effective, less expensive, more convenient or easier to administer, or have fewer or less severe
side effects, than any products that we may develop. Our competitors also may obtain FDA, EMA or other regulatory approval for
their products more rapidly than we may obtain approval for ours, which could result in our competitors establishing a strong
market position before we are able to enter the market.
Intellectual
Property
Our
success will depend in large part on our ability and that of our licensors to:
● prosecute and defend our future patents, once obtained;
Although
we rely extensively on licensing patents from third parties, we intend to seek appropriate patent protection for product candidates
in our research and development programs, where applicable, and their uses by filing patent applications in the United States
and other selected countries. We intend for these patent applications to cover, where possible, claims for compositions of matter,
medical uses, processes for preparation and formulations.
Our
current patent portfolio consists of the number of patents related to our drug candidates licensed from each third-party licensor.
In addition to the international patents and/or international and U.S. patent applications licensed from our third-party licensors,
we have licensed at least the following number of U.S. patents:
CoNCERT Yuhan Elion Aposense Akashi Total
We
are also presently evaluating the submission of two potential patents for PCS6422 and one for PCS499.
Besides
relying on patents, we also rely on trade secrets, proprietary know-how and continuing innovation to develop and maintain our
competitive position, especially when we do not believe that patent protection is appropriate or can be obtained. We seek protection
of these trade secrets, proprietary know-how and any continuing innovation, in part, through confidentiality and proprietary information
agreements. However, these agreements may not provide meaningful protection for, or adequate remedies to protect, our technology
in the event of unauthorized use or disclosure of information. Furthermore, our trade secrets may otherwise become known to, or
be independently developed by, our competitors.
License
Agreements
The
following descriptions of our license agreements are only summaries. You should also refer to the copies of such agreements which
have been filed as exhibits to this Annual Report.
License
Agreement with CoNCERT Pharmaceuticals, Inc.
On
October 4, 2017, Promet entered into a License Agreement with CoNCERT (“CoNCERT License Agreement”). On March 19,
2018, we, Promet, and CoNCERT entered into an Amended Option Licensing Agreement (“March Amendment”) that, among other
things, assigned the CoNCERT Agreement from Promet to us and we exercised the exclusive commercial license option for the PCS499
compound from CoNCERT.
The
CoNCERT License Agreement provides us with an exclusive (including as to CoNCERT) royalty-bearing license to CoNCERT’s patent
rights and Know-How to develop, manufacture, use, sub-license and commercialize compounds (PCS499 and each metabolite thereof)
and pharmaceutical products with such compounds worldwide. We are required to pay CoNCERT royalties, on a product–by-product
basis, on future worldwide net sales, or pay a percentage of any sublicense revenue.
We
will incur royalty obligations to CoNCERT on a country-by-country and product-by-product basis that expire on a country-by-country
and product-by-product basis on the later of (i) expiration or invalidation of the last patent rights covering such product in
such country or (ii) the tenth anniversary of the date of the first commercial sale to a non-sublicensee third party of such product
in such country.
We
are required to use commercially reasonable efforts, at our sole cost and expense, to develop and obtain regulatory approval for
one product in the U.S. and at least one other major market and, subject to obtaining regulatory approval in the applicable major
market, commercialize one product in the U.S. and at least one other major market. CoNCERT may terminate the agreement if, following
written notice and a 60 day opportunity to demonstrate a plan to cure, it believes that we are not using commercially reasonable
efforts to develop and obtain regulatory approval for one product in the U.S. and in at least one other major market for any consecutive
nine month period.
The
term of the CoNCERT License Agreement continues in full force and effect until the expiration of the last royalty term. On a country-by-country
and product-by-product basis, upon the expiration of the royalty term in such country with respect to such product, we shall have
a fully paid-up, perpetual, irrevocable license to such intellectual property with respect to such product in such country. In
the event of a material breach of the CoNCERT Agreement, either party may terminate the agreement provided such breach is not
cured in the 90 days following written notice of the breach (which period is shortened to 15 days for a payment breach). In addition,
either party may terminate the agreement upon an assignment for the benefit of creditors or the filing of an insolvency proceeding
by or against the other party that is not dismissed within 90 days of such filing.
License
Agreement with Yuhan Corporation
On
August 19, 2020, we entered into a License Agreement with Yuhan Corporation (“Yuhan License Agreement”), pursuant
to which we acquired an exclusive license to develop, manufacture and commercialize PCS12852 (formerly known as YH12852) globally,
excluding South Korea.
As
consideration for the Yuhan License Agreement and related Share Issuance Agreement, we issued to Yuhan 500,000 shares of common
stock. As additional consideration, we will pay Yuhan development and regulatory milestone payments (a portion of which are payable
in shares of our common stock based on the volume weighted average trading price during the period prior to such achievement and
a portion of which are payable in cash) upon the achievement of certain milestones, based on a Yuhan affiliate purchasing 750,000
shares of common stock for $3,000,000 in our October 2020 underwritten public offering. The milestones primarily consist of dosing
a patient in pivotal trials or having a drug indication approved by a regulatory authority in the United States or another country.
In addition, we must pay Yuhan one-time sales milestone payments based on the achievement during a calendar year of one or more
thresholds for annual sales for products made and pay royalties based on annual licensing sales. We are also required to split
any milestone payments received with Yuhan based on any sub-license agreement we may enter into.
In
conjunction with a joint Processa-Yuhan Board to oversee such commercialization efforts, we are required to use commercially reasonable
efforts, at our sole cost and expense, to research, develop and commercialize products in one or more countries, including meeting
specific diligence milestones that consist of: (i) preparing a first draft of the product development plan within 90 days; (ii)
requesting an FDA pre-IND meeting for a product within 6 months; (iii) dosing a first patient in a Phase 2A clinical trial with
a product within 24 months; and (iv) dosing a first patient with a product in a Phase 2B clinical trial, Phase 3 clinical trial
or other pivotal clinical trial with a product within 48 months. Either party may terminate the agreement in the event of a material
breach of the agreement that has not been cured following written notice and a 60-day opportunity to cure such breach (which is
shortened to 15 days for a payment breach).
License
Agreement with Elion Oncology, Inc.
On
August 23, 2020, we entered into a condition precedent License Agreement with Elion Oncology (“Elion License Agreement”),
pursuant to which we acquired an exclusive license to develop, manufacture and commercialize PCS6422 globally. The grant of license
was conditioned on the following being satisfied by October 30, 2020: (i) our closing on an equity financing of at least $15 million
in gross proceeds and (ii) successful up-listing to Nasdaq.
On
October 6, 2020, all conditions were satisfied, resulting in the addition of PCS6422 to the Processa portfolio, and we paid $100,000
cash and issued 825,000 shares of our common stock to Elion. Such shares are subject to a lock-up, with 50% of such shares released
from such lock up after six months and the remaining 25% tranches to be released following 9 months and 12 months, respectively.
As part of the Elion
License Agreement, we have agreed to issue to Elion 100,000 shares of our common stock on each of the first and second anniversary
dates of the Elion License Agreement. We believe the payment of these amounts is probable and represent seller financing
since the only condition related to their payment is the passage of time, which management does not believe is substantive. We
valued the shares at $4.00 per share based on the underwritten public offering price on October 6, 2020, which is the date
the conditions precedent in the license agreement were met.
As
additional consideration, we will pay Elion development and regulatory milestone payments (a portion of which are payable in shares
of our common stock and a portion of which are payable in cash) upon the achievement of certain milestones, which include FDA
or other regulatory approval and dosing a patient. In addition, we must pay Elion one-time sales milestone payments based on the
achievement during a calendar year of one or more thresholds for annual sales for products made and pay royalties based on annual
licensing sales. We are also required to split any milestone payments received with Elion based on any sub-license agreement we
may enter into.
We are required to use
commercially reasonable efforts, at our sole cost and expense, to research, develop and commercialize products in one or more countries,
including meeting specific diligence milestones that consist of: (i) dosing a first patient in a Phase 1B clinical trial with a
product within 12 months; and (ii) dosing a first patient with a product in a Phase 2 or 3 clinical trial within 48 months. Either
party may terminate the agreement in the event of a material breach of the agreement that has not been cured following written
notice and a 90-day opportunity to cure such breach (which is shortened to 15 days for a payment breach).
License
Agreement with Aposense, Ltd.
On
May 24, 2020, we entered into a condition precedent License Agreement with Aposense, Ltd. (“Aposense License Agreement”),
pursuant to which we were granted Aposense’s patent rights and Know-How to develop and commercialize their next generation
irinotecan cancer drug, PCS11T (formerly known as ATT-11T). The Aposense License Agreement provides us with an exclusive worldwide
license (excluding China), to research, develop and commercialize products comprising or containing PCS11T. The grant of license
was conditioned on the following being satisfied within nine months of May 24, 2020 (or the Aposense License Agreement shall terminate):
(i) our closing of an equity financing and successful up-listing to Nasdaq and (ii) Aposense obtaining the approval of the Israel
Innovation Authority for the consummation of the transactions contemplated by the Aposense License Agreement.
On
October 6, 2020, all conditions were satisfied, resulting in the addition of PCS11T to the Processa portfolio, and we issued 625,000
shares of our common stock to Aposense. Such shares are subject to a lock-up, with 40% of such shares released from such lock
up after six months and the remaining two 30% tranches to be released upon completion of the next two subsequent quarters. As
additional consideration, we will pay Aposense development and regulatory milestone payments (up to $3.0 million per milestone)
upon the achievement of certain milestones, which primarily consist of having a drug indication approved by a regulatory authority
in the United States or another country. In addition, we will pay Aposense one-time sales milestone payments based on the achievement
during a calendar year of one or more thresholds for annual sales for products made and pay royalties based on annual licensing
sales. We are also required to split any sales milestone payments or royalties we receive with Aposense based on any sub-license
agreement we may enter into.
License
Agreement with Akashi Therapeutics, Inc.
On
August 29, 2019, we entered into an exclusive license agreement with Akashi Therapeutics, Inc. ( “Akashi License Agreement”)
to develop and commercialize an anti-fibrotic, anti-inflammatory drug, PCS100. The Akashi License Agreement provides us with a
worldwide license to research, develop, make and commercialize products comprising or containing PCS100. As partial consideration
for the license, we paid $10,000 to Akashi upon full execution of the Akashi License Agreement. This upfront payment was expensed
as a research and development cost. As additional consideration, we will pay Akashi development and regulatory milestone payments
(up to $3.0 million per milestone) upon the achievement of certain milestones, which primarily consist of having a drug indication
approved by a regulatory authority in the United States or another country. In addition, we must pay Akashi one-time sales milestone
payments based on the achievement during a calendar year of one or more thresholds for annual sales for products made and pay
royalties based on annual licensing sales. We are also required to split any milestone payments we receive with Akashi based on
any sub-license agreement we may enter into.
We
are required to use commercially reasonable efforts, at our sole cost and expense, to research, develop and commercialize products
in one or more countries, including meeting specific diligence milestones that consist of (i) requesting a meeting with the FDA
for a first indication within 18 months of the date of the agreement, (ii) submitting an IND for a drug indication on or before
June 30, 2022 and (iii) initiating a Phase 1 or 2 trial for a drug indication on or before December 30, 2022. Either party may
terminate the agreement in the event of a material breach of the license agreement that has not been cured following written notice
and a 60-day opportunity to cure such breach (which is shortened to 15 days for a payment breach). We have not submitted a
meeting request with the FDA and are evaluating our continued involvement with Akashi.
Government
Regulation
The
FDA and comparable regulatory authorities in state and local jurisdictions and in other countries impose substantial and burdensome
requirements upon companies involved in the clinical development, manufacture, marketing and distribution of drugs, such as those
we are developing. These agencies and other federal, state and local entities regulate, among other things, the research and development,
testing, manufacture, quality control, safety, effectiveness, labeling, storage, record keeping, approval, advertising and promotion,
distribution, post-approval monitoring and reporting, sampling and export and import of our product candidates.
U.S.
Government Regulation
In
the United States, the FDA regulates drugs under the Federal Food, Drug, and Cosmetic Act, or FDCA, and its implementing regulations.
The process of obtaining regulatory approvals and the subsequent compliance with appropriate federal, state, local and foreign
statutes and regulations requires the expenditure of substantial time and financial resources. Failure to comply with the applicable
U.S. requirements at any time during the product development process, approval process or after approval, may subject an applicant
to a variety of administrative or judicial sanctions, such as the FDA’s refusal to approve pending NDAs, withdrawal of an
approval, imposition of a clinical hold, issuance of warning letters, product recalls, product seizures, total or partial suspension
of production or distribution, injunctions, fines, refusals of government contracts, restitution, disgorgement or civil or criminal
penalties.
The
process required by the FDA before a drug may be marketed in the United States generally involves the following:
● submission to the FDA of an NDA;
● satisfactory completion of an FDA advisory committee review, if applicable;
Pre-clinical
studies
Before
testing any biological product candidate in humans, including our product candidates, the product candidate must undergo rigorous
pre-clinical testing. The pre-clinical developmental stage generally involves laboratory evaluations of drug chemistry, formulation
and stability, as well as studies to evaluate toxicity in animals, to assess the potential for AEs and, in some cases, to establish
a rationale for therapeutic use. The conduct of pre-clinical studies is subject to federal regulations and requirements, including
GLP regulations for safety/toxicology studies. An IND sponsor must submit the results of the pre-clinical studies, together with
manufacturing information, analytical data, any available clinical data or literature and a proposed clinical protocol, to the
FDA as part of the IND.
An
IND is a request for authorization from the FDA to administer an investigational product to humans and must become effective before
human clinical trials may begin. Some long-term pre-clinical testing, such as animal tests of reproductive AEs and carcinogenicity,
may continue after the IND is submitted. An IND automatically becomes effective 30 days after receipt by the FDA, unless the FDA
raises concerns or questions before that time related to one or more proposed clinical trials and places the trial on clinical
hold. In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before the clinical trial can begin. As
a result, submission of an IND may not result in the FDA allowing clinical trials to commence.
Clinical
trials
The
clinical stage of development involves the administration of the investigational product to healthy volunteers or patients under
the supervision of qualified investigators, generally physicians not employed by, or under control of, the trial sponsor, in accordance
with GCPs, which include the requirement that all research patients provide their informed consent for their participation in
any clinical trial. Clinical trials are conducted under protocols detailing, among other things, the objectives of the clinical
trial, dosing procedures, subject selection and exclusion criteria and the parameters to be used to monitor subject safety and
assess efficacy. Each protocol, and any subsequent amendments to the protocol, must be submitted to the FDA as part of the IND.
Furthermore, each clinical trial must be reviewed and approved by an IRB for each institution at which the clinical trial will
be conducted to ensure that the risks to individuals participating in the clinical trials are minimized and are reasonable in