PCI Biotech - Småprat 4 (PCIB) 1

[lenny]

Data fra vaksinen skal komme dette året. Studiestart var 27.07.2017.

Skrevet 18.06.2020:

The company’s lead program, A001, is in Phase I/II tests to treat metastatic melanoma with data expected next year.

http://www.chinabiotoday.com/articles/etherna-raises-38-million

// 1 JUNE 2019

Safety and immune stimulation data from an intranodal delivery of TriMix mRNA, in the adjuvant melanoma study E011-MEL

Niel (Belgium)

eTheRNA immunotherapies NV (Niel, Belgium) announces that Dr. Ana Arance, Medical Oncologist at Hospital Clinic de Barcelona, will present safety and immune response data from the E011-MEL study at the ASCO (American Society of Clinical Oncology) Annual Meeting during the poster session “Developmental Immunotherapy and Tumor Immunobiology” on 01 June 2019. The study E011-MEL investigated the safety and immunogenicity of a mRNA-based immunotherapy ECI-006. ECI-006 is a combination of mRNAs encoding for the dendritic cell maturation triple mRNA TriMix together with mRNA coding for5 tumor-associated antigens, which aims to elicit an immune response against the tumor. Since the patients had been radically operated on, there was no expected, immediate clinical activity read-out.

The primary goal of the study was to study whether the injection of ECI-006 into inguinal or axillary lymph nodes was tolerable and clinically feasible. The intranodal injections were performed in the clinic under ultrasound guidance without anesthesia. There were two treatment arms, each of 10 patients. One group received a dose of 600 µg and the other a dose of 1800 µg per injection. The study was performed in centres in Belgium and Spain.

Nineteen out of 20 patients completed the treatment. One patient discontinued the study after 4 doses due to disease relapse. Administration of ECI-006 was well tolerated in all patients with no serious side effects. ELISPOT and intracellular cytokine staining were performed on T cells pre-stimulated in vitro for 10-12 days. Vaccine-induced immune responses were detected in 4/10 and 3/10 patients treated with the low and high dose, respectively.

Dr Arance commented “it is very encouraging that we see immune responses against most of the antigens used in the vaccine. Clinically this therapy was eminently well tolerated and feasible. Future studies should include patients with metastatic disease and test whether dosing with a concomitant check-point inhibitor can be additive”

Dr Bertil Lindmark, CMO of eTheRNA Immunotherapies stated “The study showed that intranodal therapy is clinically feasible and well tolerated. Specific Immune responses in 35% of the patients in the adjuvant setting gives a good basis for coming studies in metastatic melanoma on top of a checkpoint inhibitor”

Kilde: News | Archive 2019 | eTheRNA immunotherapies NV

[StockDZ]

Seems Ukraine is recruiting now

onco.in.ua - лечение опухолей в Харькове

Критерии включения

[LCY]

Prøvde lengre oppe å få en forklaring på ‘Intranodal injection’ men det gikk ikke, ser nå det det blir injisert inn i en lymfe-node. Er vi sikker på att det er forenlig med Vacc belysning?
Fikk inntrykk av at lymfe-nodene ligger for dypt for belysning av den plaster-boksen?

Om denne leverings metoden er prøvd ut i 20 pasienter som beskrevet i @lenny 's siste post utelukker vel det FimaVacc?
Tumor-lytic som Investor beskrev virker mer lovende, men ser ikke ut som om de er kommet så langt med det?
Gleder meg veldig til presentasjonene neste uke men synes det blir litt mye haleluja nå.

Edit: Så E011-MEL studien ett par poster over var uten FimaVacc, men de nevner videre studier med en CPI i tillegg, så da er det ingenting i veien for å bytte levering også går jeg ut fra.
Vanskelig for en lekmann å holde følge her, men mulig hype-toget har noe for seg likavel da.

[Jubel]

What a beautiful day

Ok, I’ll wake you up at ATH

[StockDZ]

At these price levels I prefer to sleep please wake me up at 80NOK O’clock

[lenny]

Fra utdrag fra fimaVacc patentet 21 januar 2020, som PW har uttalt klart og tydelig var et viktig patent for PCIB. Hvorfor det? Legg merke til ordet CYTOKINES

Oslo (Norway), 21 January 2020 – PCI Biotech (OSE: PCIB), a cancer focused biopharmaceutical company, today announces that the U.S. Patent and Trademark Office (USPTO) has granted the company a US patent covering the use of fimaVacc in combination with cytokines.

The combination of cytokines with PCI Biotech’s vaccine technology, fimaVacc, has been shown to be effective for enhancing cellular immune responses that are important for the effect of therapeutic vaccines. The now granted US patent gives broad coverage for the combination of various cytokines with the fimaVacc technology.

Effective induction of cytotoxic T-cells will be critical to realise the huge potential of therapeutic cancer vaccines, but vaccines often fail to generate such responses. Insufficient delivery of vaccine antigens to the appropriate presentation pathway in the immune cells may be one of the main reasons for weak cytotoxic T-cell responses. The fimaVacc technology has the potential to effectively enhance vaccine presentation through these pathways.

Kilde: PCI Biotech: US patent granted for the vaccine technology (fimaVacc) in combination with cytokines | GlobeNewswire

Så til et poster fra eTheRNA sin NAKED MRNA Melanoma vaksine, som viser stort fokus på T-celle respons og C Y T O K I NE S:

Kan også laste ned PDF her:

Poster-CIMT-2019-final.pdf

Clinically this therapy was eminently well tolerated and feasible. Future studies should include patients with metastatic disease and test whether dosing with a concomitant check-point inhibitor can be additive”

Dr Bertil Lindmark, CMO of eTheRNA Immunotherapies stated “The study showed that intranodal therapy is clinically feasible and well tolerated. Specific Immune responses in 35% of the patients in the adjuvant setting gives a good basis for coming studies in metastatic melanoma on top of a checkpoint inhibitor”

Kilde: News | Archive 2019 | eTheRNA immunotherapies NV

Det begynner å bli mange fellesnevnere. Noe jeg har glemt?

• Samarbeid eTheRNA-PCIB siden 2016
• Naked mRna delivery
• Melanoma (patent fimaVacc granted)
• Patent fimaVacc cytokines januar 2020
• Fokus på T-celle respons (CD8) og cytokines i vaksine (se poster)

[KrissKross]

Takk for den fabelaktige jobben du gjør, Lenny.

[Investor1]

Hva kan dette dreie seg om i verdier om det mye klaffer?

[Syvcys]

De to indikasjonene som er diskutert her, er ikke hva Ultimovacs holder på med i 2 av sine fase 2 studier. Henholdsvis INTIUM OG FOCUS?

[Jubel]

Naked mRNA teknologi er svært verdifullt om det viser gode resultater. Kan dette overføres til annen mRNA behov og erstatte løsning med leveringsteknologi som brukes i dag og med bivirkninger (typisk lipid) er det kanskje litt sånn: tenk på et tall! Enorme muligheter og mulige verdier. Snøffelen lagde en oversikt over dealer innen mRNA, store verdier. Men first thing first! Klarer PCIB det som Lenny og flere graver opp over er det STORT. Liten tvil om det.

Ta en titt på hva Moderna prises til😅

[lenny]

Spennende og voksende marked både:

Melanoma:

HPV vaksiner:

Hva PCIB er verdt tørr jeg ikke spekulere i her inne, men markedet burde kanskje bevege seg en smule over emisjonskursen hvis man bruker grunnleggende sannsynlighetsberegning…

[lenny]

Jeg vil minne om hva PW sa sist podcast, at vi skulle lytte til han.

Januar 2020 kommenterte han fimaVacc patentet slik i børsmeldingen:

There are many vaccines under development utilising cytokines to elicit immune responses. The US patent granted today is important for PCI Biotech’s development strategy, as it supplements our ability to generate an internal future vaccine pipeline, in addition to bringing value for the fima Vacc technology in partnering efforts, said Per Walday, CEO of PCI Biotech.

Da skal jeg drømme om cytokines, immune responses, vaccine pipeline, value for fimaVacc og partnering i natt!

[lenny]

Hvorfor en mRNA vaksine kan trenge fimaVacc, kan forstås ut fra artikkelen under:

https://www.nature.com/articles/nrd.2017.243

Den er fryktelig lang, men inneholder mange spennende fakta som peker mot at fimaVacc har et enormt marked:

Før man leser noen av utdragene under, kan man starte med hvordan artikkelen definerer adjuvant:

An additive to vaccines that modulates and/or boosts the potency of the immune response, often allowing lower doses of antigen to be used effectively. Adjuvants may be based on pathogen-associated molecular patterns (PAMPs) or on other molecules that activate innate immune sensors.

Så til noen utdrag av artikkelen, hvor blant annet naked mRNA, cytokiner og T-celle respons nevnes flere steder:

The immunostimulatory properties of mRNA can conversely be increased by the inclusion of an adjuvant to increase the potency of some mRNA vaccine formats. These include traditional adjuvants as well as novel approaches that take advantage of the intrinsic immunogenicity of mRNA or its ability to encode immune-modulatory proteins. Self-replicating RNA vaccines have displayed increased immunogenicity and effectiveness after formulating the RNA in a cationic nanoemulsion based on the licensed MF59 (Novartis) adjuvant50. Another effective adjuvant strategy is TriMix, a combination of mRNAs encoding three immune activator proteins: CD70, CD40 ligand (CD40L) and constitutively active TLR4. TriMix mRNA augmented the immunogenicity of naked, unmodified, unpurified mRNA in multiple cancer vaccine studies and was particularly associated with increased DC maturation and cytotoxic T lymphocyte (CTL) responses (reviewed in Ref. 51). The type of mRNA carrier and the size of the mRNA–carrier complex have also been shown to modulate the cytokine profile induced by mRNA delivery. For example, the RNActive (CureVac AG) vaccine platform52,53 depends on its carrier to provide adjuvant activity. In this case, the antigen is expressed from a naked, unmodified, sequence-optimized mRNA, while the adjuvant activity is provided by co-delivered RNA complexed with protamine (a polycationic peptide), which acts via TLR7 signalling52,54. This vaccine format has elicited favourable immune responses in multiple preclinical animal studies for vaccination against cancer and infectious diseases18,36,55,56. A recent study provided mechanistic information on the adjuvanticity of RNActive vaccines in mice in vivo and human cells in vitro54. Potent activation of TLR7 (mouse and human) and TLR8 (human) and production of type I interferon, pro-inflammatory cytokines and chemokines after intradermal immunization was shown54. A similar adjuvant activity was also demonstrated in the context of non-mRNA-based vaccines using RNAdjuvant (CureVac AG), an unmodified, single-stranded RNA stabilized by a cationic carrier peptide57.

Development of prophylactic or therapeutic vaccines against infectious pathogens is the most efficient means to contain and prevent epidemics. However, conventional vaccine approaches have largely failed to produce effective vaccines against challenging viruses that cause chronic or repeated infections, such as HIV-1, herpes simplex virus and respiratory syncytial virus (RSV). Additionally, the slow pace of commercial vaccine development and approval is inadequate to respond to the rapid emergence of acute viral diseases, as illustrated by the 2014–2016 outbreaks of the Ebola and Zika viruses. Therefore, the development of more potent and versatile vaccine platforms is crucial.

As no toxic effects were observed in mice or non-human primates, clinical trials using this approach to treat patients with advanced melanoma or triple-negative breast cancer have been initiated (NCT02410733 and NCT02316457).

The combination of mRNA vaccination with adjunctive therapies, such as traditional chemotherapy, radiotherapy and immune checkpoint inhibitors, has increased the beneficial outcome of vaccination in some preclinical studies

While preclinical studies have generated great optimism about the prospects and advantages of mRNA-based vaccines, two recent clinical reports have led to more tempered expectations22,91. In both trials, immunogenicity was more modest in humans.

The future of mRNA vaccines is therefore extremely bright, and the clinical data and resources provided by these companies and other institutions are likely to substantially build on and invigorate basic research into mRNA-based therapeutics.

Avslutter med denne kavalkaden bilder fra gårsdagens høydepunkter:

Og en publikasjon av Sjoerd van der Burg (Advisory PCIB), om kreftvaksiner, T-celler, antigen, cytikiner etc. Forklarer kanskje hvordan han ble fascinert av PCIB:

«each of these cytokines has the capacity to expand antigen-experienced T cells»

https://www.jci.org/articles/view/80009

[Ruben2]

“Therapeutic cancer vaccines” ( en av veldig mange publikasjoner ) med SH van der Burg ble allerede i 2014 sitert av 349 fremstående vitenskapsfolk, Hen er åpenbart en av de aller største i sin verden. Kanskje den største, Litt av et kupp å få han som rådgiver…og årsaken gir seg selv.

[Newman]

En børsspekulant fra Benin
tenkte som så: “Cytokin
pluss litt mRNA
gjør at syke blir bra,
Og kursen blir ren kokain!”

[Stupet]

Fantastisk gravearbeid @lenny
Om dette er tilfellet så ser det ut som rammene er satt og dette snart presenteres markedet?
Spennende tider

[Ted]

I Q3-2019 nevnte PW om fimaVacc - “lisens til flere partnere / mulig eksklusive partnere”.

Hva vil en slik lisens avtale med eTheRNA til bruk på Melanomia eller HPV kunne gi av inntekter/royalties per behandling?

Kan vi forvente upfront betaling når de går inn i fase 3 studier med Melanomia?

Er det en kommersiell avtale som blir kunngjort neste uke?

[Jubel]

Konferanser viser stort sett eller alltid til presentasjoner med resultater. Ser PCI Biotech er sponsor og det kan antas at resultater vil være oppsiktsvekkende og gode .

Deretter kan det ved interessante resultater bli «kamp» om teknologien. Altså deretter mulig avtaler i en eller annen form (altså sjelden avtaler meldes under en konferanse). Men alt kan selvsagt skje. Jeg har ingen fasit.

En spekulasjon er at AZ har «sin» mRNA teknologi og prestisje gjennom ressursbruk og eierskap i Moderna

Pfizer har sin prestisje gjennom samarbeid BioNTech.

Disse mRNA teknologiene prises hinsides.

Vi vet alle PCIB sin mcap…

eTheRNA har kanskje sin prestisje og ressursbruk mot PCIB? Og det ser ut til at eiere i eTheRNA har bidratt med midler tidligere til selskapsformål. Kan det tenkes at de vil gjøre som AZ? Ha delvis eierskap?

Og hvem har den beste leveringsteknologien naked mRNA? Mulig forskjellig effekt til ulikt bruk. Men det skulle ikke forundre meg om det er rom for flere løsninger innen det hotteste i biotek?! mRNA og leveringsteknologi

[Columna]

Pcib i Radium i dag?

[sjog]

eTheRNA er ikke i en slik finansiell posisjon at de kan gjøre noen stor deal med PCIB.