| Organization and Description of the Business |
Note
1 – Organization and Description of the Business
Business
Activities and Organization
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 for which few
or no treatment options currently exist. We currently have five drugs: four in various stages of clinical development (PCS499, PCS12852,
PCS3117 and PCS6422) and one in nonclinical development (PCS11T). We group our drugs into non-oncology (PCS499 and PCS12852) and oncology
(PCS3117, PCS6422 and PCS11T). A summary of each drug is provided below:
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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 completed a Phase 2A trial for PCS499 in patients with ulcerative and non-ulcerative necrobiosis lipoidica
(NL) in late 2020, and in May 2021 we enrolled the first patient in our Phase 2B trial for the treatment of ulcerative NL. We expect
to complete our interim analysis and complete enrollment of the Phase 2B trial by the end of 2022; and, depending on the results,
begin a pivotal Phase 3 trial in 2023. |
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PCS12852
is a highly specific and potent 5HT4 agonist which has already been evaluated in clinical studies in South Korea for gastric emptying
and gastrointestinal motility. In October 2021, the FDA cleared our IND application to proceed with a Phase 2A trial for the treatment
of gastroparesis. We anticipate beginning to enroll patients in the first half of 2022, complete enrollment in the second half of
2022 and complete final analysis in the first half of 2023. |
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PCS3117,
which we licensed in June 2021, is a cytosine analog, similar to gemcitabine (Gemzar®) but different enough in chemical structure
that some patients are more likely to respond to PCS3117 than gemcitabine. We are evaluating biomarkers to elucidate specifically
which patients are more likely to benefit from PCS3117 compared to gemcitabine and other chemotherapy agents to provide a more targeted,
precision medicine approach to the treatment of various types of cancer, such as pancreatic and/or non-small cell lung cancer. Over
the next 6-12 months, we will be developing, refining and qualifying these biomarker assays for use in our clinical trials as well
as define the potential paths to approval for different types of cancer. We anticipate initiating a Phase 2B or adaptive designed
Phase 3 in 2023. |
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PCS6422
is an orally administered irreversible enzyme inhibitor administered in combination with capecitabine. When combining capecitabine
with PCS6422 (the “Next Generation Capecitabine”), capecitabine becomes a more potent cancer chemotherapy agent than
current FDA approved capecitabine. On August 2, 2021, we enrolled the first patient in our Phase 1B dose-escalation maximum
tolerated dose trial in patients with advanced refractory gastrointestinal (GI) tract tumors and our interim analysis of Cohorts 1
and 2 found no dose-limiting toxicities (DLTs), no drug related adverse events greater than Grade 1, and no hand-foot syndrome. In
addition, the interim analysis revealed when PCS6422 inhibits DPD enzyme activity, 5-FU metabolism is significantly decreased
(<10% metabolized to F-Bal compared to typically 80%) and the potency of capecitabine is significantly increased (at least 50
times greater 5-FU potency based on systemic exposure per mg of capecitabine administered). The single dose of PCS6422, however, did
not sustain the DPD inhibition throughout 7 days of capecitabine dosing which was needed to maintain the improved potency of
capecitabine. Therefore, we have modified the existing protocol to obtain more data on DPD inhibition and de novo formation. We
anticipate that this additional data will allow us to select PCS6422 dosage regimens that will maintain DPD inhibition for each
patient treated with this Next Generation Capecitabine (i.e., combination of PCS6422 and capecitabine). After interacting with the
FDA and making protocol modifications, we expect to restart the Phase 1B study in the second quarter of 2022 and complete enrollment
while defining the Next Generation Capecitabine regimen (i.e., the PCS6422 regimens and the corresponding capecitabine regimens) by
the end of 2022. We expect that our overall timeline has not changed with a Phase 2B or 3 trial starting in 2023-2024 and NDA
submission in 2027-2028. |
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Our
only nonclinical drug candidate is PCS11T, an analog of SN38 (SN38 being the active metabolite of irinotecan) and a next generation
irinotecan drug for multiple types of cancers. PCS11T is presently in the IND pre-clinical toxicology stage. We hope to submit an
IND in the first half of 2023, followed by a Phase 1B maximum tolerated dose trial. |
Impact
of COVID-19
We
have experienced delays in the enrollment of patients in our PCS499 Phase 2B trial due to COVID-19. Potential patients have died from
COVID-19 prior to screening and continue to be reluctant to travel to our testing sites for fear of contracting COVID-19. Delays in enrollment
lengthen the time of studies and increase their costs. The COVID-19 pandemic has created uncertainties
in the expected timelines for clinical stage biopharmaceutical companies such as ours, including possible delays in clinical trials and
disruptions in the supply chain for raw materials used in clinical trial work. Such delays could materially impact our business in future
periods. Furthermore, the spread of COVID-19, which has caused a broad impact globally, may materially affect us economically. For more
information on the risks associated with COVID-19, refer to Part I, Item 1A, “Risk Factors.”
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