Ultimovacs (ULTI) Fundamentale forhold

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@Laaarsas

Borde inte sambandet mellan HR och antal events vara säkert?

Det er her du har misforstått. Hazard Ratio er ikke et enkelt forholdstall basert på antall eventer. Det er arealet mellom de to KM-plottene, slik at tidspunktene for eventene har noe å si. Man må altså bruke hele plottene for å få riktig svar. @Boblegutten sine simuleringer (som @ketilaaj baserer seg på over her) gir nok ganske så presise svar for mest sannsynlige HR ved forskjellig antall eventer både i NIPU og INITIUM, som også stemmer med både artikkelen til Helland om NIPU, og hva selskapet har kommunisert opp igjennom om begge studiene. Å faktisk regne det ut “manuelt” er ganske så komplisert, noe man fort forstår om ser på denne: Proportional hazards model - Wikipedia

[TekBot]

Ultimovacs Provides 3-Year Update from Phase I Study in Malignant Melanoma: Results Confirm Strong Overall Survival in Patients Treated with UV1 Cancer Vaccine

• All patients in cohort 2 who were alive after 2 years remain alive after 3
  years

…

Vis børsmeldingen

Oslo, 19 June 2023: Ultimovacs ASA (“Ultimovacs”) (OSE ULTI), a clinical-stage
biotechnology leader in novel immunotherapeutic cancer vaccines, today announced
encouraging overall survival (OS) data from the cohort 2 in the UV1-103 Phase I
clinical trial in malignant melanoma. All patients in cohort 2 who were alive at
the 2-year follow-up, remain alive at the 3-year follow-up.

The UV1-103 study evaluates Ultimovacs’ universal cancer vaccine, UV1, in
combination with the anti-PD-1 checkpoint inhibitor pembrolizumab, as first-line
treatment in patients with advanced non-resectable or metastatic malignant
melanoma. The study enrolled 30 patients in the U.S. in two cohorts that
differed only in the concentration of GM-CSF used as vaccine adjuvant. 27 of
these patients agreed to long-term monitoring after 2 years.

At 3-year follow-up across the two cohorts, 67% (18/27) of patients were still
alive. 3-year overall survival in cohort 1 was 71% (12/17), including one
patient death between years 2 and 3 as reported in October 2022. 3-year overall
survival in cohort 2 was 60% (6/10).

Ultimovacs has previously reported data showing a complete response rate in the
UV1-103 study of 33% (complete disappearance of tumors) and an objective
response rate of 57% (complete or partial disappearance of tumors). Biomarker
analyses reported in October 2022 showed robust clinical responses in patients
treated with the combination of UV1 and pembrolizumab, regardless of patients’
PD-L1 status. The safety profile of UV1 in combination with pembrolizumab is
comparable to that of pembrolizumab alone.

“We are very encouraged to observe a 67% overall survival rate at 3-year follow-
up in this Phase I study, which treats the same patient population as our UV1
Phase II study, INITIUM. These data further strengthen the previously reported
results from the study, including good safety for UV1 and remarkable 33%
complete response rate in patients with metastatic malignant melanoma where
surgery is not an option. The data continue to show that UV1 in combination with
pembrolizumab has promising signs of efficacy,” said Jens Bjørheim, Chief
Medical Officer at Ultimovacs. “We are looking forward to receiving more data
from the UV1 clinical trials, to advance UV1 further to the benefit of cancer
patients.”

Ultimovacs further investigates UV1 in malignant melanoma in its randomized
Phase II INITIUM trial of UV1 in combination with ipilimumab and nivolumab. The
trial completed enrollment of 156 patients with advanced non-resectable or
metastatic malignant melanoma in July 2022. The top-line results will be
disclosed after cancer progression has been verified in 70 patients, which was
anticipated in the first half of 2023. As announced in April 2023, the readout
is now expected in the second half of 2023. This is due to patients taking
longer than estimated to experience cancer progression, which is very
encouraging and positive for patients.

==ENDS==

About the UV1-103 phase I trial in Malignant Melanoma

This US-based Phase I clinical trial is evaluating the Company’s lead candidate,
UV1, in combination with the anti-PD-1 checkpoint inhibitor, pembrolizumab, as a
first-line treatment in patients with unresectable metastatic malignant
melanoma. The trial evaluates safety, tolerability, and initial signs of
clinical response. Thirty patients in the U.S. were treated in the study in two
cohorts that differed only in the concentration of GM-CSF used as vaccine
adjuvant. The 20 patients in the first cohort received a 37.5 mcg GM-CSF
adjuvant dose per UV1 vaccination. The 10 patients in the second cohort received
the standard 75 mcg GM-CSF adjuvant dose per UV1 vaccination. The study has
completed the enrollment of 30 patients, as announced on August 18, 2020. All
included patients received the drugs as first line treatment for advanced and
metastatic malignant melanoma.

Compiled clinical results for the 30 patients enrolled are:

• Objective response rate (ORR): 57%. Complete response rate (CR): 33%
• Median Progression Free Survival (mPFS): 18.9 months (as measured by
  iRECIST)
• Overall survival (OS) after 12 months: 87% (26/30). OS after 24 months: 73%
  (22/30). OS after 36 months: 67% (18/27). Out of the 9 deaths, 4 happened
  during the first year, 4 during the second year, and one during the third
  year across both cohorts.

Patients will continue to be followed up for long-term survival. Three patients
in cohort 1 chose not to be followed up further after 24 months. The trial had
previously reached its primary endpoint of safety and tolerability, and no
unexpected safety issues related to UV1 have been observed in this trial.

As a historical reference (not head-to-head comparison since dosing and the
patient population is different), the registration study Keynote-006 for
pembrolizumab showed an overall survival rate of 51% at 36 months.

The U.S. Food and Drug Administration (FDA) granted a dual Fast Track
designation for UV1 in combination with checkpoint inhibitors in the treatment
of unresectable or metastatic melanoma - either as add-on therapy to
pembrolizumab or as add-on therapy to ipilimumab. Ultimovacs is currently
evaluating UV1 as add-on therapy to ipilimumab and nivolumab as first-line
treatment of patients with unresectable or metastatic melanoma in the phase II
study INITIUM.

About Ultimovacs

Ultimovacs is a clinical-stage biotechnology leader in novel immunotherapeutic
cancer vaccines with broad applicability. Ultimovacs’ lead cancer vaccine
candidate UV1 is directed against human telomerase (hTERT) an antigen that is
present in 85-90% of cancers in all stages of tumor growth. A broad clinical
program, with Phase II trials in five cancer indications enrolling more than
670 patients, aims to demonstrate UV1’s impact in combination with other
immunotherapies in multiple cancer types expressing telomerase and where
patients have unmet medical needs. UV1 is universal, off-the-shelf and easy to
use, and is a patented technology owned by Ultimovacs.

In addition, Ultimovacs’ adjuvant platform, based on the proprietary Tetanus-
Epitope-Targeting (TET) technology, combines tumor-specific antigens and
adjuvant in the same molecule and is in Phase I clinical development.

About UV1

UV1 is a universal cancer vaccine designed to induce a specific T cell response
against telomerase. UV1 consists of long, synthetic peptides, representing a
sequence in the reverse transcriptase subunit of telomerase (hTERT), shown to
induce CD4+ T cells. These CD4+ T cells have the potential to provide
inflammatory signals and T cell support believed to be critical for triggering a
strong anti-tumor immune response. Following intradermal injection, antigen
presenting cells (APCs) in the skin are exposed to the vaccine peptides. These
APCs will process the peptides, and present vaccine epitopes on Human Leukocyte
Antigen (HLA) molecules to naïve T cells in the lymph nodes. Activated vaccine
specific T cells will then enter the circulation and search for cells displaying
their cognate antigen in the context of HLA molecules.

The UV1 peptides contain several epitopes, shown to be non-restrictive in terms
of (HLA) alleles for presentation. It is therefore not required to perform HLA
pre-screening of patients, which potentially enables broad population
utilization of the vaccine. UV1 is administered over three months as eight
intradermal injections together with the immune-modulator GM-CSF.

For further information, please see www.ultimovacs.com or contact:

Carlos de Sousa, CEO
Email: carlos.desousa@ultimovacs.com (mailto:carlos.desousa@ultimovacs.com)
Phone: +47 908 92507

Anne Worsøe, Head of Investor Relations
Email: anne.worsoe@ultimovacs.com (mailto:anne.worsoe@ultimovacs.com)
Phone: +47 90686815

This information is considered to be inside information pursuant to the EU
Market Abuse Regulation and is subject to the disclosure requirements pursuant
to Section 5-12 in the Norwegian Securities Trading Act.

This stock exchange announcement was published by Anne Worsøe, Head of IR at
Ultimovacs ASA, on 19 June, 2023 at 07:00 am CET.

Kilde

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Det var jo en kjærkommen god nyhet

Jeg hadde imidlertid et lite håp om at Bjørnheim hadde realisert gamle CEO sitt mantra “the fact that you are alive is not considered clinical data”, for tallene nå er naturligvis fortsatt preget av de tre som trakk seg fra videre “oppfølging” i kohort 1.

Oppdatert oversikt.

OS	KEYNOTE-006	kohort 1 (n=20)	kohort 2 (n=10)	kohort 1+2 (n=30)
12mnd	68 %	85% (17)	90% (9)	87% (26)
18mnd	63 %	80% (16)	?
24mnd	58 %	80% (16)	60% (6)	73% (22)
36mnd	51 %	71% (12/17)	60% (6/10)	67% (18/27)
48mnd	46 %
60mnd	43 %

[Sjakk]

Er det en nothingburger eller skal det leses som “the fact that you are dead is considered clinical data” ? (tror denne diskusjonen har vært oppe før, men jeg husker ikke konklusjonen)

[h3nk1]

Vi fikk nylig vår første synlige short i aksjen (Details - Short Sale Register). På Oslo Børs er det ikke mange igjen å velge blant for hedgefondene, så det var påregnelig.

I alle tilfelle, forrige uke det ble laget en liten presentasjon for å oppsummere “grunnfjellet” fra fundamentaltråden når det kommer til INITITUM (og dels NIPU). Denne ble delt med nevnte shortaktør og enkelte andre interessenter før helgen.

Med andre ord helt OK timing med mer melanomdata i dag.

I sin helhet og til deling:
2023-06-14 Information on Ultimovacs relevant to active short positions and buy-side (OSE) - external.pdf (652,6 KB)

Det bør kile godt i serken å syne INITIUM med shortposisjon. I det hele tatt burde det kile for alle som står utenfor. Winning odds in plain sight.

[Syvcys]

Shorten ble vel satt 0906 på ca 80 på 0.52% ifølge DN investor. De turte ikke å shorte på 120 før NIPU melding, men altså ca 80 etter meldingen syntes de var en god ide, dem om det!!

[novalusus]

Dette innlegget ble rapportert og er midlertidig skjult.

[AdG]

Nei, helt uenig. Her har vi et medikament som dekker et stort ikke møtt klinisk behov. Sammenligningen din blir som å se på epler og elefanter

[novalusus]

Dette innlegget ble rapportert og er midlertidig skjult.

[gado1]

Du vil ikke heller kommentere/chatte med NorskTippings kundeservice, istedenfor å fylle denne tråden med din kunnskap?

[h3nk1]

Kan moderator (@Evilfreud) rydde opp og denne typen innlegg tas i småprat. Mvh.

[AdG]

Spill lotto du! Så kan vi som står hver dag på alle vakter med denne pasientgruppen glede oss over at vi har fått et nytt og særdeles kraftig verktøy i verktøyskuffen vår

[Laaarsas]

Jag vet att HR är arean mellan två kurvor. Hur har man då tagit fram värdena för “simplified method”? Vilken input har man förutom antal events och antal patienter i varje arm?

[Hod]

Bare så alle har det klart: har BMS fått full innsikt i studien eller kun topline på NIPU?

[h3nk1]

Topline, mulig de kan få «noe» mer under NDA? Det vet andre best. Akademikerne eier dataene, så i hvilken grad de eventuelt kan dele noe mer utover topline er jo et litt interessant spørsmål.

[anon69684326]

@h3nk1

Topline

Hva betyr “topline”?

[abacus]

Nettstedet lawinsider.com definerer “top line data” slik når det gjelder rapportering av resultater fra kliniske studier;

Top-Line Data Definition | Law Insider

[Boms]

Og med disse eksemplene kan vi vel være enige om at Ultimovacs IKKE leverte på sitt løfte om å offentliggjøre Top-Line data for NIPU i 1H23 slik de sa i alle sine presentasjoner. De ga riktignok “konklusjonen” på data, og når de nå sier at dataene ikke er noe de har “eier” og derfor ikke kan offentliggjøre, har de enkelt nok lovet mer enn de kan holde og det har ødelagt enormt for kursen - dessverre.

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For nye lesere og folk som ikke gidder å sette seg inn i, forstår eller har troen på modellen til @ketilaaj - noen veldig enkle fakta om INITIUM:

• Den høyeste enden av 95% konfidensintervallet for mPFS er høyest av alle historiske sammenligninger i CheckMate-067 med 19,3 måneder. Det er derfor veldig usannsynlig at mPFS for studien som helhet er høyere enn 19,3 måneder dersom UV1 ikke har effekt.

• Studien leser av når 70 av 156 pasienter har fått progresjon - altså godt under/i god tid før median

• Det er i dag 21 måneder siden pasient nummer 78 ble innrullert (median oppfølgingstid), og de 156 pasientene har en gjennomsnittlig oppfølgingstid på 21,5 måneder.

[Roc]

Erfaringsmessig, hovedproblemet med investigator initierte studier er at slike studier (oftest) representerer en større risiko for biotek/farma enn de vanligvis ville ha tatt selv.

Investigatorene vil ofte forske på en indikasjon som representerer høyere risiko enn det biotek/BP selv ville tatt. I tillegg er slike forskerinitierte studier ofte under powered, færre sites og endepunkt som kanskje er for optimistiske.

Forskere vil gjerne få data raskest mulig dvs vise effekt av et utprøvende legemiddel og hjelpe pasientene raskest mulig, mens biotek/farma må balansere dette opp mot risikoen for å genere negative data og dermed risiko for å sette et potensielt lovende legemiddel i større risiko enn nøvendig.

Greit å ha dette i mente; at de som kjenner legemidlet best er også de som har lengst kvernet på å lage et utviklignsløp som optimaliserer mulighetene for suksess.