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Psorilax:Come sbarazzarsi di |crema fai da te per psoriasi

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Psorilax:Come sbarazzarsi di |crema fai da te per psoriasi

CREMA TRATTAMENTO PSORIASI OFFERTA -50% !

Psorilax: prezzo, funziona, recensioni, opinioni, composizione

The following discussion is intended to assist in the understanding and
assessment of significant changes and trends related to our results of
operations and our financial condition together with our consolidated
subsidiaries. This discussion and analysis should be read in conjunction with
the accompanying unaudited financial statements and our Annual Report on Form
10-K for the year ended December 31, 2019 filed with the SEC on March 5, 2020
("2019 Form 10-K"), which includes additional information about our critical
accounting policies and practices and risk factors. Historical results and
percentage relationships set forth in the statement of operations, including
trends which might appear, are not necessarily indicative of future operations.



Overview


Provectus is a clinical-stage biotechnology company developing a new class of
drugs for oncology, hematology, and dermatology based on an entire,
wholly-owned, family of chemical small molecules called halogenated xanthenes.
Intratumoral (aka intralesional) PV-10®, the first small molecule autolytic
immunotherapy, which can induce immunogenic cell death, is undergoing clinical
study for adult solid tumor cancers, such as melanoma and GI tumors (e.g.,
hepatocellular carcinoma, metastatic colorectal cancer, metastatic
neuroendocrine tumors, metastatic uveal melanoma), and preclinical study for
pediatric solid tumor cancers (e.g., neuroblastoma, Ewing sarcoma,
rhabdomyosarcoma, osteosarcoma) and blood cancers (e.g., acute myeloid
leukemia). Topical PH-10® is undergoing clinical study for inflammatory
dermatoses (e.g., psoriasis, atopic dermatitis).



La nostra scienza e tecnologia di base




Oncology. PV-10 drug product is an injectable formulation of rose bengal
disodium (4,5,6,7-tetrachloro-2',4',5',7'-tetraiodofluorescein disodium salt)
("RB") drug substance (i.e., active pharmaceutical ingredient). PV-10 is a
bright rose red solution containing 10% w/v RB in 0.9% saline for injection,
which is supplied in single-use glass vials containing 5 mL (to deliver) of
solution. PV-10 is administered directly to superficial disease (e.g., cutaneous
melanoma) via injection and to visceral disease (e.g., GI tumors) via
image-guided percutaneous injection. PV-10 selectively accumulates in the
lysosomes of cancer cells. Cancer cells, particularly advanced cancer cells, are
very dependent on effective lysosomal functioning (Piao et al., Ann N Y Acad Sci
2016). Cancer progression and metastasis are associated with lysosomal
compartment changes (Nishimura et al., Pathol Oncol Res 1998; Gocheva et al.,
Genes Dev 2006), which are closely correlated with, among other things, invasive
growth, angiogenesis, and drug resistance (Fahrenbacher et al., Cancer Res
2005). Physicochemical properties of lysosomes trap PV-10. Lumenal pH of 4.5 to
5 is ideal for the conversion of soluble rose bengal disodium into insoluble
rose bengal lactone.



Lysosomes are the central organelles for intracellular degradation of biological
macromolecules and organelles. Discovered by Christian de Duve, M.D. in 1955,
lysosomes have been linked with a number of biological processes like cell
death, inflammasome activation, and immune response. In 1959, Dr. de Duve
described lysosomes as "suicide bags," because their rupture led to cell death
and tissue autolysis. Lysosomes have been shown to play a role in each of the
primary pathways of cell death, which are apoptosis, autophagy, and necrosis. He
was awarded the Nobel Prize in 1974 for discovering and characterizing
lysosomes.



Provectus showed that PV-10 selectively accumulates in the lysosomes of cancer
cells and disrupts them, causing the cancer cells to die. PV-10 (RB) has also
been shown by Provectus and independent researchers to trigger each major,
distinct form of lysosomal cell death; that is, apoptosis, autophagy, and
necrosis.



  14





Il targeting lisosomiale di PV-10 comprende:

? Transiting del plasmalemma (cioè la membrana cellulare) delle cellule tumorali. PV-10

penetra nella membrana cellulare delle cellule cancerose che normalmente protegge il

cellula cancerosa dal suo ambiente circostante. PV-10, tuttavia, è escluso da

    normal cells;

  ? Accumulating in the lysosomes of cancer cells. As noted above, the
    physicochemical properties of lysosomes trap PV-10;

? Attivazione del rilascio di contenuti lisosomiali. L'autolisi acuta può verificarsi all'interno

60 minuti. Primi lavori preclinici di Provectus sul targeting lisosomiale di PV-10

ha mostrato risposte identiche in diversi modelli di malattia, come Hepa1-6 murino

carcinoma epatocellulare, carcinoma mammario umano HTB-133 e H96Ar umano

carcinoma polmonare a piccole cellule multi-farmaco resistente;

? Indurre la rapida morte cellulare delle cellule tumorali. Esclusione anticipata del blu tripan

il lavoro di Provectus ha confermato la morte cellulare entro poche ore; e,

? Consistenza del pH intracellulare con rilascio di contenuti lisosomiali acidi.

Confermati i primi lavori di colorazione seminaphthorhodafluor-1 (“SNARF-1”) di Provectus

    lower intracellular pH upon exposure to PV-10 (RB).




Dermatology. For psoriasis, pathways significantly improved include published
psoriasis transcriptomes and cellular responses mediated by IL-17, IL-22, and
interferons. Clinical work has shown that more than 500 disease-related genes
were down-regulated after four weeks of PH-10 application and expression of a
wide-range of central "psoriasis related" genes including IL-23, IL-17, IL-22,
S100A7, IL-19, IL-36, and CXCL1 were effectively normalized; that is, treated
lesional skin had values in the same range as baseline non-lesional skin.



La nostra strategia di sviluppo di farmaci per oncologia ed ematologia




The Company's strategy is to (i) demonstrate the independent action of
single-agent PV-10; that is, safety and activity in T cell and non-T cell
inflamed tumor types, in high and low tumor mutation burden tumor types, and in
other tumor type categories, such as gene mutations, (ii) demonstrate the
coordinated induction of multiple immune signaling pathways (i.e., functional
immunogenic cell death ("ICD"); Snyder et al., Sci Immunol 2019) by PV-10
treatment, (iii) demonstrate the functional T cell response generated by PV-10
treatment, and (iv) contrast and compare PV-10 treatment - safety, activity, and
induced immune response - with that of immune checkpoint inhibition ("CI") and
other drug classes in single-agent and PV-10-based combination therapy settings.



This strategy may quicken the advancement of single-agent PV-10 along a
pathway-to-approval in solid tumor cancer indications where there is high unmet
need, limited activity from other therapies, and the opportunity to display the
immune response from PV-10 treatment, such as neuroendocrine tumors ("NET")
metastatic to the liver ("mNET") (NCT02693067). This strategy may also permit
the Company to develop and advance a cancer combination therapy involving one or
more CI and/or other drug classes along a pathway-to-approval in a disease
indication where there is high unmet need, limited activity from standard of
care ("SOC") treatment, and the opportunity to display how PV-10 augments
clinical response to existing or emerging SOCs, such as uveal melanoma
metastatic to the liver ("mUM") (i.e., combination therapy with an anti-CTLA-4
agent and an anti-PD-1 agent) (NCT00986661).



In ematologia, i collaboratori della ricerca continuano a sviluppare il loro lavoro preclinico
un potenziale vaccino contro la leucemia a base di PV-10 per pazienti pediatrici.

La nostra strategia di sviluppo di farmaci per la dermatologia




The Company's strategy is to (i) demonstrate 12-week single-agent administration
proof-of-concept ("POC") for PH-10 that includes (a) a preclinical safety study
of extended 12-week administration (compared to, previously, four weeks), (b) a
clinical mechanism of action study in atopic dermatitis, which would be a
"book-end" trial to the already completed clinical mechanism study in psoriasis,
(c) Phase 2 randomized controlled trials of PH-10 for the treatment of psoriasis
and atopic dermatitis that may potentially utilize SOC comparators, and (d)
end-of-Phase 2 meetings with the FDA upon the completion of the abovementioned
Phase 2 trials, and (ii) expand POC PH-10 treatment to include dermatology
combination therapy. Our goal for this POC work is to achieve Phase 3
trial-ready status for PH-10 in both psoriasis and atopic dermatitis.



  15





Componenti dei risultati operativi

Spese di ricerca e sviluppo




A large component of our total operating expenses is the Company's investment in
research and development activities, including the clinical development of our
product candidates. Research and development expenses represent costs incurred
to conduct research and undertake clinical trials to develop our drug product
candidates. These expenses consist primarily of:



  ? Costs of conducting clinical trials, including amounts paid to clinical
    centers, clinical research organizations and consultants, among others;
  ? Salaries and related expenses for personnel, including stock-based
    compensation expense;
  ? Other outside service costs including cost of contract manufacturing;
  ? The costs of supplies and reagents; and,
  ? Occupancy and depreciation charges.



Spendiamo i costi di ricerca e sviluppo sostenuti.




Research and development activities are central to our business model. We expect
our research and development expenses to increase in the future as we advance
our existing product candidates through clinical trials and pursue their
regulatory approval. Undertaking clinical development and pursuing regulatory
approval are both costly and time-consuming activities. As a result of known and
unknown uncertainties, we are unable to determine the duration and completion
costs of our research and development activities, or if, when, and to what
extent we will generate revenue from any subsequent commercialization and sale
of our drug product candidates.



Spese generali e amministrative




General and administrative expense consists primarily of salaries, stock-based
compensation expense and other related costs for personnel in executive,
finance, accounting, business development, legal, information technology and
corporate communication functions. Other costs include facility costs not
otherwise included in research and development expense, insurance, and
professional fees for legal, patent and accounting services.



  16






Results of Operations


Confronto dei tre mesi terminati 31 marzo 2020 e 31 marzo 2019



Overview



Total operating expenses were $1,448,240 for the three months ended March 31,
2020, a decrease of $348,344 or 19.4% compared to the three months ended March
31, 2019. The decrease was driven primarily by our continued transformation and
process improvement efforts within the Company. Net loss for the three months
ended March 31, 2020 was $1,827,061, an increase of $457,231 or 33.4% which was
primarily attributable to gains recognized in connection with settlements of
lawsuits in 2019.



                                        For the Three Months Ended
                                                 March 31,                 Increase/
                                           2020              2019         (Decrease)       % Change

Operating Expenses:
Research and development              $      909,446$  1,037,331$  (127,885 )        -12.3 %
General and administrative                   538,794          759,253        (220,459 )        -29.0 %
Total Operating Expenses                   1,448,240        1,796,584        (348,344 )        -19.4 %

Total Operating Loss                      (1,448,240 )     (1,796,584 )      (348,344 )         19.4 %
Other Income/(Expense):
Gain on settlement of lawsuits                     -          675,000        (675,000 )       -100.0 %
Research and development tax credit           26,251           84,072         (57,821 )        -68.8 %
Investment and interest income                    79            2,255      
   (2,176 )        -96.5 %
Interest expense                            (405,151 )       (334,573 )       (70,578 )         21.1 %
Total Other Income/(Expense)               (378,821)          426,754       (805,575)        -188.8  %

Net Loss                              $   (1,827,061 )$ (1,369,830 )$   457,231          -33.4 %



Spese di ricerca e sviluppo

Research and development expenses were $909,446 for the three months ended March
31, 2020, a decrease of $127,885 or 12.3% compared to the three months ended
March 31, 2019. The decrease was primarily due to (i) reduced cost on clinical
trials due to closure of MM-31 study, and (ii) a decrease in payroll and related
taxes due to a lower negotiated employment agreement.



La seguente tabella riassume le nostre spese di ricerca e sviluppo sostenute
durante i tre mesi finiti 31 marzo 2020 e 31 marzo 2019:



                                         For the Three Months Ended
                                                  March 31,                 Increase/
                                           2020               2019         (Decrease)       % Change

Operating Expenses:
Research and development:
Clinical trial and research expenses   $     584,057$   627,535$   (43,478 )          -6.9 %
Depreciation/amortization                    169,942           169,942     
         -             0.0 %
Insurance                                     73,592            65,963           7,629            11.6 %
Payroll and taxes                             66,479           149,475         (82,996 )         -55.5 %
Rent and utilities                            15,376            24,416     

(9.040) -37,0%
Ricerca e sviluppo totali $ 909.446$ 1.037.331$ (127,885) -12,3%




  17





Spese generali e amministrative




General and administrative expenses were $538,794 for the three months ended
March 31, 2020, a decrease of $220,762 or 29.1% compared to the three months
ended March 31, 2019. The decrease was primarily due to (i) lower legal fees as
we concluded the Company's lawsuits against former accounting vendors, (ii) a
decrease in payroll and related taxes, and (iii) lower professional fees.



La seguente tabella riassume le nostre spese generali e amministrative sostenute
durante i tre mesi finiti 31 marzo 2020 e 31 marzo 2019:



                                           For the Three Months Ended
                                                   March 31,                  Increase/
                                             2020               2019         (Decrease)       % Change

Operating Expenses:
General and administrative:
Depreciation                            $        1,361$     1,361     $         -             0.0 %
Directors fees                                  96,250            96,250               -             0.0 %
Insurance                                       41,866            48,396          (6,530 )         -13.5 %
Legal and litigation                            88,062           193,641        (105,579 )         -54.5 %
Other general and administrative cost           17,007            22,895   
      (5,888 )         -25.7 %
Payroll and taxes                               35,486           123,271         (87,785 )         -71.2 %
Professional fees                              250,011           260,212         (10,201 )          -3.9 %
Rent and utilities                               7,660            12,439          (4,779 )         -38.4 %
Foreign currency translation                     1,091               788             303            38.5 %

Totale generale e amministrativo $ 538.794$ 759.253

 $  (220,459 )         -29.0 %




Other Income/(Expense)



Other income decreased by $734,997 from $761,327 for the three months ended
March 31, 2019 to $26,330 for the three months ended March 31, 2020 which was
primarily attributable to gains recognized in connection with settlements of
lawsuits in 2019.


Gli interessi passivi sono aumentati di $ 70.578 a partire dal $ 334.573 per i tre mesi finiti
31 marzo 2019 per $ 405.151 per i tre mesi finiti 31 marzo 2020. Il
l'aumento è dovuto all'aumento del numero di obbligazioni convertibili pagabili
in sospeso in relazione alle note PRH.

Liquidità e risorse di capitale

Our cash and cash equivalents were $213,739 at March 31, 2020, compared to
$590,706 at December 31, 2019. The condensed consolidated financial statements
and notes thereto included in this Quarterly Report on Form 10-Q have been
prepared on a basis that contemplates the realization of assets and the
satisfaction of liabilities and commitments in the normal course of business. We
have continuing net losses and negative cash flows from operating activities. In
addition, we have an accumulated deficit of $235,643,889 as of March 31, 2020.
These conditions raise substantial doubt about our ability to continue as a
going concern for a period within one year from the date that the financial
statements included elsewhere in this Quarterly Report on Form 10-Q are issued.
Our financial statements do not include any adjustments to the amounts and
classification of assets and liabilities that may be necessary should we be
unable to continue as a going concern. Our ability to continue as a going
concern depends on our ability to obtain additional financing as may be required
to fund current operations.



Management's plans include selling our equity securities and obtaining other
financing to fund our capital requirement and on-going operations, including the
2020 Financing; however, there can be no assurance we will be successful in
these efforts. The financial statements do not include any adjustment that might
be necessary if we are unable to continue as a going concern. Significant funds
will be needed to continue and complete our ongoing and planned clinical trials.



The SARS-CoV-2 pandemic has already caused significant disruptions in the
financial markets, and may continue to cause such disruptions, which could
impact our ability to raise additional funds and may also impact the volatility
of our stock price and trading in our stock. Moreover, the pandemic has also
significantly impacted economies worldwide, which could result in adverse
effects on our business and operations. We cannot be certain what the overall
impact of the SARS-CoV-2 pandemic will be on our business. It has the potential
to adversely affect our business, financial condition, results of operations,
and prospects.



  18






Access to Capital



Management plans to access capital resources through possible public or private
equity offerings, including the 2020 Financing, exchange offers, debt
financings, corporate collaborations or other means. If we are unable to raise
sufficient capital through the 2020 Financing or otherwise, we will not be able
to pay our obligations as they become due.



The primary business objective of management is to build the Company into a
commercial-stage biotechnology company; however, we cannot assure you that
management will be successful in implementing the Company's business plan of
developing, licensing, and/or commercializing our prescription drug product
candidates. Moreover, even if we are successful in improving our current cash
flow position, we nonetheless plan to seek additional funds to meet our current
and long-term requirements in 2020 and beyond. We anticipate that these funds
will otherwise come from the proceeds of private placement transactions,
including the 2020 Financing, the exercise of existing warrants and outstanding
stock options, or public offerings of debt or equity securities. While we
believe that we have a reasonable basis for our expectation that we will be able
to raise additional funds, we cannot assure you that we will be able to complete
additional financing in a timely manner. In addition, any such financing may
result in significant dilution to stockholders.



Critical Accounting Policies


Per una descrizione dei nostri principi contabili critici, vedere la Nota 3 – Critica
Politiche contabili nella parte 1, voce 1 della presente relazione trimestrale sul modulo 10-Q.

Principi contabili emessi di recente

I principi contabili emessi di recente sono inclusi nella Nota 3 – Critico
Politiche contabili nella parte 1, voce 1 della presente relazione trimestrale sul modulo 10-Q.

Disposizioni fuori bilancio

Non abbiamo accordi fuori bilancio, finanziamenti o altro
rapporti con entità non consolidate o altre persone, noto anche come
entità per scopi speciali (“SPE”).

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CREMA TRATTAMENTO PSORIASI OFFERTA -50% !