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, 2019filed with the SECon 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 Duvedescribed 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
Overview Total operating expenses were
$1,448,240for the three months ended March 31, 2020, a decrease of $348,344or 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, 2020was $1,827,061, an increase of $457,231or 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
$909,446for the three months ended March 31, 2020, a decrease of $127,885or 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
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
Ricerca e sviluppo totali
Spese generali e amministrative
General and administrative expenses were
$538,794for the three months ended March 31, 2020, a decrease of $220,762or 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
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
$ (220,459 )-29.0 % Other Income/(Expense) Other income decreased by $734,997from $761,327for the three months ended March 31, 2019to $26,330for the three months ended March 31, 2020which was primarily attributable to gains recognized in connection with settlements of lawsuits in 2019.
Gli interessi passivi sono aumentati di
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
$213,739at March 31, 2020, compared to $590,706at 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 $235,643,889as 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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