Ja. 60 events. 60 i eksperimentell arm (gemcis + Amphinex) og 60 med kun gemcis. Totalt 120 pasienter. Hele studien er med 186 pasienter jf
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En fersk aksjonærliste for PCIB er tilgjengelig for Insider-medlemmer. Ikke Insider? Les mer og prøv gratis
De har byttet fra PFS til ORR som måleparameter for interimanalysen. Det betyr at tidbruken ikke lenger er drevet av hendelser/events, men av rekrutteringstakten. ORR sjekkes på fastsatte tidspunkt etter behandling. Det betyr også at de da vil inkludere et nokså likt antall fra begge gruppene i analysen, i motsetning til før da man forventet/håpet på flere hendelser i kontrollgruppen. Har selskapet sagt eksplisitt hvor mange de nå ser for seg er nødvendige for å gjøre interimanalysen?
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Nytt endepunkt for interim er orr. Har ikke sett info på ant pas - events utgår.
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Nei. Men fra q4 står det “The modification is not expected to have significant impact on the estimated timelimes”.
Videre står der: " The planned change for the interim analysis is not yet included in the overview below, as the protocol amendment is still in progress". Da får vi vel info om dette når protokollen er endret.
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En ting som er litt interessant er at ORR er et endepunkt som får rimelig mye kjeft av mange av de konservative innen biotech fordi det oppleves som svakt og alt for lett å oppnå, og ikke nødvendigvis sier så mye om nytten av medisinen.
Mens i gallegangskreft så vet jo vi at det er rimelig binært, er gallegangen åpen eller er den det ikke.
Så det er veldig bullish for pcib aksjen at byttet har skjedd.
Og det herlige er jo at RELEASE kombinerer det beste fra to verdener. ORR i interim og randomised control på en gang.
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Jeg tror overgangen til ORR kan innebære utfordringer av to anledninger:
-
Non-measureable disease kan ikke inngå (noe det kunne i PFS)
-
Stable disease forskjeller hensynstas ikke av målet (mens forskjellen ville tydelig framgå i PFS).
Første punkt reduserer antall events man kan få pr. inkluderte pasient. Andre punkt reduserer takten i hvilket man kan se forskjell mellom gruppene.
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Ikke glem at PFS er sekundært endepunkt og vil inngå som viktig parameter for statistikeren og monitoreringskomiteen. De vil også se på OS og alle parametrene vil sees i sammenheng og støtte opp om vurderingen.
De vil nok også se til DCR (Disease Control Rate), som hensyntar SD.
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Absolutt, det blir en helhetsvurdering. Funker behandlingen godt (som vi tror) skal det nok vise seg.
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FDA skriver dette:
Surrogate endpoints for accelerated approval must be reasonably likely to predict clinical
benefit (FD&C Act § 506©(1)(A);
21 CFR part 314, subpart H
; and 21 CFR part 601, subpart
E).
While durable ORR has been used as a traditional approval endpoint in some
circumstances, ORR has also been the most commonly used surrogate e
ndpoint in support of
accelerated approval.
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Vi vet at cohort 4 hadde ORR på 50% og ABC-02 hadde ca 20% ORR (men kun 1/13 i sammenliknbar populasjon!). Men la oss beholde disse tallene og se på hvor mange pasienter man trenger for å bevise en statistisk signifikans.
Kjørte en helt enkel test her på et online tool du finner på nettet , og man får faktisk signifikant forskjell på 50 vs 20 helt ned mot 30 pasienter i hver gruppe!
https://www.evanmiller.org/ab-testing/chi-squared.html#
Hvis man har slike data og det støttes opp av forskjell i Kaplan-Meier på PFS og OS, så er det slett ikke umulig at kontrollarmen kan brytes av lenge før det er rekruttert 120 pasienter.
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Er det lagt opp til avlesning og analyse underveis av “Key investigator leader”?
(Er dette noe vi håper på, eller er det åpen kontakt mellom myndigheter og forskere gjennom hele studiet)
1 Like
Ikke av KOL, men av en monitoreringskomite, som består av blant annen en statistiker. Denne komiteen er de eneste som har tilgang til dataene underveis. De har rett og plikt til å informere selskapet om de ser ting som bør få konsekvens for studiet, som feks at det er veldig stor forskjell mellom armene slik at det ikke er etisk forsvarlig å fortsette den ene armen.
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Gjelder denne prosedyren for alle typer studier?
(relevans for andre studier/selskaper)
For å supplere det @Investor skriver.
Studien er blinda overfor PCIB. Selskapet skal bare følge opp de enkelte klinikkene ved nødvendig leveranse av fimaporfin og laserlys. Før rekruttering kan starte, altså som et ledd i aktiveringsprosessen, vil representanter gå nøye gjennom studieoppsett og prosedyrer.
Så er det slik at nevnte komité (Independent Data Monitoring Committee) er den som “sjekker ut” at behandlingen har tildredsstillende sikkerhet (safety and toxicity). Dette skjer etter at åtte pasienter i den eksperimentelle armen (PCI-armen) har mottatt dobbel behandling.
En annen sentral aktør i gjennomføringen av studien er Contract Research Organisation (CRO). Denne er kontrahert av PCIB for oppfølging av klinikkene, administrativt.
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Ny artikkel fra Hong Kong som henviser til våre data
Novel technology has been tested, such as photochemical internalization (PCI). PCI is a light-based method and is employed to trigger the endosomal escape of RIP. Saporin linked with a photosensitizer functionalized CPP showed cytotoxicity augmentation in MC28 fibrosarcoma cells [135]. Another study also showed that the cytotoxicity of IT 225.28-saporin was strengthened by using PCI with a photosensitizer disulfonated tetraphenyl chlorin (TPCS2a)
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For de som tviler
Studie fra Italia ; )
https://www.iris.unina.it/handle/11588/723508#.XmpThiWUmEc
Importantly, drug codelivery in NPs was very efficient in inducing cell mortality also in DTX resistant HeLa-R cells overexpressing P-glycoprotein 1 in which the dose of the chemotherapeutic can be reduced by more than 100 times using DTX/TPCS2a-NPs. Overall, our data demonstrate that the protocol for the preparation of HA-targeted double layer polymeric NPs allows to control the concentration ratio of coloaded drugs and the delivery of the transported drugs for obtaining a highly synergistic interaction combining DTX-chemotherapy and TPCS2a-PDT.
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Vil du kort si hva denne handler om? 
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I disse dager hvor vi diskuterer mulig avtale med AZ så er det kanskje greit om vi tar en oppgang hvordan PCI Biotech har prøvd å sikre seg retten til bruk av teknologien.
Oppsummert så har jeg funnet:
11 innvilgede patenter
6 som kan bli godkjent når som helst…
Av de seks som er under vurdering, så stammer 4 fra tidsrommet 2016 til 2018 (publisering) og jeg antar det vil følge med en børsmelding om de går gjennom (ref Per som også venter på avklaring).
https://patents.justia.com/patent/20180050105
https://patents.justia.com/patent/20170143811
https://patents.justia.com/patent/20160206725
https://patents.justia.com/patent/20160040128
De resterende to er fra 2011 og 2009.
La oss tenke oss at vi sitter i AZ management og ser på gamle studier, pågående studier, egne studier samt PCIB sitt patent bibliotek med opsjon på at seks andre kan gå gjennom. I tillegg kan det være flere, siden publisering skjer kun etter 18mnd fra innlevering. Kjøperen, hvem nå enn det blir får tilgang til denne unike patent-poolen samtidig så nærmer vi oss mulig markedstilgang. I tillegg så har vårt unike team vært innvolvert i utrolig mye som enda ikke er patentert / publisert …
La oss ta en enkel sammenlikning - NANO. NANO har kun to patenter som stammer fra 2014/2016. De har ikke flere «publication» av det jeg kan se. Tror Roy har hoppet videre : ).
Patenter
Compound and method
https://patents.justia.com/patent/10537639 Date of Patent : Jan 21, 2020
The present invention provides a method of expressing an antigenic molecule or a part thereof on the surface of a cell using a photochemical internalization method in which a cytokine, preferably GM-CSF, is used to enhance the method. The method may be used to stimulate an immune response and for various therapeutic or prophylactic methods…
Antigen delivery device and method
https://patents.justia.com/patent/10166401 Date of Patent : Jan 1, 2019
A device for activating light-induced rupture of endocytic vesicles in target cells of a patient so as to effect delivery of an administered antigen to cytosol in the target cells, is described. The device is adapted to be worn by a patient over a region of skin where an antigen and a photosensitising agent are to be administered. The device comprises a rear surface that is rounded or otherwise configured to be worn against the patient’s skin…
Method of stimulating an immune response
https://patents.justia.com/patent/9737594 Date of Patent : Aug 22, 2018
The present invention provides a method of stimulating an immune response to an antigenic molecule, by contacting a cell with the antigenic molecule and with a photosensitizing agent, irradiating the cell, and thereby presenting the antigenic molecule, or part thereof, on the surface of said cell and stimulating an immune response.
Conjugate of a photosensitiser and chitosan and uses thereof
https://patents.justia.com/patent/9901636 Date of Patent : Feb 27, 2018
The present invention relates to novel chitosan-based conjugates, e.g. nanocarriers, comprising a derivative of the biocompatible polymer chitosan conjugated to a photosensitizing agent, and uses thereof in photochemical internalization (PCI) and photodynamic therapy (PDT). The invention also relates to the use of the novel conjugates of the invention in treatment or prevention of diseases, particularly cancer, and for vaccination purposes.
Method for introducing siRNA into cells by photochemical internalisation
https://patents.justia.com/patent/9700622 Date of Patent : Jul 11, 2017
The present invention relates to a method for introducing an siRNA molecule into the cytosol of a cell, said method comprising i) contacting said cell with an siRNA molecule, a carrier and a photosensitizing agent, and ii) irradiating the cell with light of a wavelength effective to activate the photosensitizing agent, wherein said carrier comprises a cationic polyamine such as a lipopolyamine in a non-liposomal formulation, polyethyleneimine (PEI), a betacyclodextrin amine polymer, an amine group containing dendrimer, and a cationic peptide.
Photochemical internalisation of kinase inhibitors
https://patents.justia.com/patent/9241996 Date of Patent : Jan 26, 2016
The present invention relates to a method for enhancing the activity of kinase inhibitors in target cells, and more specifically for enhancing the activity of tyrosine kinase inhibitors (TKIs), said method comprising contacting a cell with a kinase inhibitor and a photosensitizing agent and irradiating said cell with light of a wavelength effective to activate the photosensitizing agent, and to the use of this method for enhancing the effects of kinase inhibitors or kinase inhibitor-based drugs in particular to achieve cell death, for example, in cancer treatment and other diseases or conditions in which kinase inhibitors, such as TKIs, have a beneficial effect.
Photosensitizing compositions
https://patents.justia.com/patent/9026203 Date of Patent : May 5, 2015
The invention relates to pharmaceutically acceptable salts of amphiphilic photosensitizing agents which have a water solubility of at least 0.5 mg/ml and to their use in methods of photochemical internalization. Such salts may be formed from a pharmaceutically acceptable base, for example an organic amine such as an amino alcohol, or from a pharmaceutically acceptable acid, for example a sulphonic acid or a sulphonic acid derivative.
Method of vaccination
https://patents.justia.com/patent/8216587 Date of Patent : Jul 10, 2012
The present invention provides a method of expressing an antigenic molecule or a part thereof on the surface of an antigen-presenting cell, said method comprising introducing a molecule into the cell cytosol by photochemical internalisation, wherein said molecule, or a part thereof, is subsequently presented on the surface of said cell. Methods of vaccination comprising this method, together with compositions comprising said cells and uses involving said cells expressing antigenic molecules are also provided.
Compound
https://patents.justia.com/patent/8096419 Date of Patent : Jan 17, 2012
he present invention provides photosensitizing agents obtained by reducing a single double bond in the porphyrin macrocycle of a sulphonated meso-tetraphenylporphyrin, preferably a disulphonated meso-tetraphenylporphyrin such as TPPS2a. The resulting sulphonated meso-tetraphenyl chlorins include compounds of formula I: (wherein X is —SO3H; n, p, q and r are each independently 0 or 1; and the sum of n, p, q and r is an integer from 1 to 4, preferably at least 2, e.g. 2 or 4) isomers and isomer mixtures thereof. The compounds of the invention and their pharmaceutically acceptable salts find particular use as photosensitizing agents in the photochemical internalization of molecules and in photodynamic therapy.
PHOTOCHEMICAL INTERNALIZATION FOR DELIVERY OF MOLECULES INTO THE CYTOSOL
https://patents.justia.com/patent/20070274953 Date of Patent : Aug 30, 2011
The present invention provides a method for introducing a molecule into the cytosol of a cell in which the cell is contacted with a photosensitising agent, the cell is irradiated with light of a wavelength effective to activate the photosensitising agent and, substantially at the same time or after the irradiation, the cell is contacted with the molecule to be introduced, particularly for use in cancer treatment, gene therapy and vaccination.
Photochemical internalization for virus-mediated molecule delivery into the cyosol
https://patents.justia.com/patent/7521239 Date of Patent : Apr 21, 2009
A method for introducing a molecule into the cytosol of a cell in which the cell is contacted with a photosensitizing agent, the cell is irradiated with light of a wavelength effective to activate the photosensitizing agent and, substantially at the same time or after the irradiation, the cell is contacted with the molecule to be introduced, particularly for use in cancer treatment, gene therapy and vaccination.
21 Likes
Publication (fra publisering til innvilget patent tar det typisk 2 til 5år )
METHOD
https://patents.justia.com/patent/20180050105 Publication Date : Feb 22, 2018
The invention concerns a method of generating an immune response in a subject, comprising administering to the subject an antigenic molecule, a photosensitizing agent, a checkpoint inhibitor, and irradiating said subject with light of a wavelength effective to activate the photosensitizing agent to generate an immune response. Preferably the method is a method of vaccination…
METHOD OF TREATING MELANOMA
https://patents.justia.com/patent/20170143811 Publication Date : May 25, 2017
The present invention relates to a method of treating or preventing melanoma using vaccination or immunisation, wherein said vaccination or immunisation involves the use of a photosensitizing agent, a melanoma antigen (i.e. an antigenic molecule), for example a vaccine component, and irradiation with light of a wavelength effective to activate the photosensitizing agent. The invention also relates to said photosensitizing agent and melanoma antigen for use in such a method, and to cells produced by the method.
COMPOUND AND METHOD FOR VACCINATION AND IMMUNISATION
https://patents.justia.com/patent/20160206725 Publication Date : Jul 21, 2016
A method of vaccination or immunisation involving the use of a photosensitizing agent, an antigenic molecule, e.g. a vaccine component, and an agent which enhances the effect of photochemical internalization (PCI)-mediated vaccination is disclosed wherein the agent is a ligand for a Toll-like receptor (TLR), and irradiation is with light of a wavelength effective to activate the photosensitizing agent. Antigenic, e.g. vaccine compositions, useful in such a method are also disclosed along with a method of generating antigen presenting cells which may be used to generate an immune response based on introducing antigenic molecules, e.g. vaccine components, into cells to achieve antigen presentation. The invention also provides methods of achieving vaccination in a subject using such cells.
METHOD
https://patents.justia.com/patent/20160040128 Publication Date : Feb 11, 2016
The present invention provides an in vitro method of expressing an antigenic molecule or a part thereof on the surface of a dendritic cell using a PCI method with TPCS2a at a concentration of 0.020-0.1 μg/ml, using light of a wavelength of between 400 and 500 nm. Methods of treatment such as vaccination comprising this method, together with compositions comprising said cells and uses involving said cells expressing antigenic molecules are also provided.
Method for Introducing a Pna Molecule Conjugated to a Positively Charged Peptide into the Cytosol and/or the Nucleus by Photochemical Internalisation (Pci)
https://patents.justia.com/patent/20110171184 Publication Date : Jul 14, 2011
The present application relates to a method for introducing a PNA molecule into the cytosol, preferably the nucleus of a cell, comprising contacting said cell with a PNA molecule and a photosensitising agent, and irradiating the cell with light of a wavelength effective to activate the photosensitising agent, wherein said PNA molecule is conjugated to a positively charged peptide. Compositions comprising such conjugated PNA molecules, cells made using the method and uses of the method are also described.
METHOD FOR INTRODUCING SIRNA INTO CELLS BY PHOTOCHEMICAL INTERNALISATION
https://patents.justia.com/patent/20090297487 Publication Date : Dec 3, 2009
The present invention relates to a method for introducing an siRNA molecule into the cytosol of a cell, said method comprising i) contacting said cell with an siRNA molecule, a carrier and a photosensiting agent, and ii) irradiating the cell with light of a wavelength effective to activate the photosensitising agent, wherein said carrier comprises a cationic polyamine such as a lipopolyamine in a non-liposomal formulation, polyethyleneimine (PEI), a betacyclodextrin amine polymer, an amine group containing dendrimer, and a cationic peptide.
24 Likes