Nykode Therapeutics (Vaccibody) Fundamentale forhold (VACC)

[Boms]

Utover sjefen for kreftforskningen ved OUS sin optimisme rundt Vaccibody sin teknologi er det vel disse avsnittene i artikkelen som er viktig å bite seg merke i:

Terapeutisk vaksine

Samarbeidet vil teste vaksinen for de som har utviklet aggressiv livmorhalskreft. For pasientene vil det si at man kan får en vaksine i armen flere ganger.

Med en terapeutisk vaksine tilsetter man noe som allerede finnes i kreftcellene, og får immunforsvaret til å gjenkjenne kreftcellene som har dette i seg. Da vil immunforsvaret drepe kreftcellene.

– Kort fortalt, så fjerner Roche sin vaksine den bremsen som gjør at immunforsvaret gir opp kampen mot kreften, mens vår vaksine sørger for at riktig immunforsvar tar seg av kreften.

Kan komme i 2023

Vaccibody regner med å begynne å behandle pasienter med den nye samarbeidsvaksinen rundt nyttår 2019. Da blir det omtrent 50 personer som kan prøve ut den nye kreftvaksinen.

– Vi planlegger å behandle alle innen et år. Da kan vi få ganske raske data på hvor godt det fungerer, sier Fredriksen.

Dersom vaksinen har en dramatisk effekt, kan man komme fortere inn på markedet og begynne å behandle pasienter. Fungerer vaksinen bra, kan man derfor forvente å se den på markedet mellom år 2023 og 2025.

– Det er flere andre som går den veien nå, fordi forståelsen for immunterapi har kommet i det siste. Tidligere har mange kreftvaksiner stanget mot veggen fordi man har forsøkt å få immunforsvaret til å reagere på kreftceller samtidig som friske celler. Og det er vanskelig.

Så langt har Vaccibody ikke hatt noen problemer med bivirkninger, og Roche sin medisin har nå i mars blitt godkjent for bruk i trippel negativ brystkreft tilfeller i USA så den er det også grunn til å anta er sikker. Jeg tror derfor vi kan anta kombinasjonen også vil være safe, og at studien derfor har en god sannsynlighet for å lykkes.
Vaccibody har hittil levert on-time og med bedre resultater enn forventet på alt de har satt i gang, og 2023-25 er faktisk ikke så lenge til. Så dette er en spennende utvikling både for pasienter og aksjonærer.

Når det gjelder vurderingen av aksjen, så er jo HPV vaksinen VB10.16 bare et av produktene til Vaccibody, og det potensielt mest verdifulle er den persontilpassede neoantigen vaksinen som kan brukes i en mengde kreftformer.

Det er vrient å lage noen sikre regnestykker på det kommersielle potensialet til Vaccibody. Prisingen av medisinen er jo en stor ukjent X, men produksjonskostnaden av den standardiserte VB10.16 vaksinen oppgis å være lav, og også være rimelig enkel og håndtere. Kostnaden for å analysere og produsere den individuelle VB10.NEO vaksinen blir selvsagt noe helt annet, men de har i løpet av fase 1 studien hatt en 100 % suksessrate i produksjonen av vaksinen. Så det ser ut til at de får til den praktiske delen av den studien.

PS!
Link til pressemelding fra Roche om godkjennelse for bruk innen brystkreft: https://www.roche.com/media/releases/med-cor-2019-03-11.htm
Tecentriq / atezolizumab er i fase 2 for bruk i livmorhalskreft.

[Mml]

Morgendagens FA:

HELSE:Vaccibody skrur opp prisingen nye 30 prosent, og nå ser kreftvaksine­selskapet mot børs slik at Jan Haudemann-Andersen kan synliggjøre en kjempegevinst.

– Vi har nå gått ut og sagt at vi innen 12 måneder skal vurdere børsnotering, sier styreleder Tom E. Pike i Vaccibody til Finansavisen.

Selskapet gjorde nylig en emisjon på 230 millioner kroner. Til tross for at selskapet igjen skrudde prisingen kraftig i været, rapporterer de om stor interesse fra både nye og eksisterende investorer.

Jan Haudemann-Andersen har vært med i en årrekke og er selskapets største private aksjonær med aksjer for hele 166 millioner kroner.

Prising: 2,2 mrd.

Ved årsskiftet 2016/2017 var hele selskapet priset til 400 millioner kroner før en emisjon på 220 millioner. Det tilsvarte 12,50 kroner pr. aksjer. I fjor vår var emisjonskursen satt til 31 kroner, og selskapet var priset til 1,5 milliarder. Nå er kursen hevet til 40 kroner, og selskapet fremstår med en prising på nær 2,2 milliarder kroner etter emisjonen.

– Emisjonskursen er basert på handel i aksjen i mellom­tiden. Aksjen er omsatt på dette nivået i forkant av emisjonen, sier Pike.

Vaccibody er ikke notert på noen markedsplass, men handles sporadisk i meglerapparatet. Emisjonen ble gjennomført med ABG Sundal Collier og Arctic Securities som finansielle rådgivere.

Gevinst: 130 mill.

Jan Haudemann-Andersen har uansett vært med på en formidabel reise. Investoren gikk inn i selskapet i 2014 – da sammen med såkornselskapet Sarsia Seed, Radiumhospitalets Forskningsstiftelse, universitets- og sykehusselskapet Inven2 og Kreftforeningen.

Den gang var selskapet priset til 42 millioner kroner før penger og 78 etter, hvilket tilsvarte en aksjekurs på drøye 3 kroner. Det innebærer at Haudemann-Andersen må ha brukt rundt 10 millioner kroner på å tilegne seg aksjeposten på den gang 12,9 prosent i selskapet. Senere har han deltatt noe i etterfølgende emisjons­runder, men ikke økt aksjeantallet vesentlig. Følgelig er hans kostpris særdeles lav.

Når selskapet går på børs ligger det følgelig an til at Haudemann-Andersen vil få synliggjort verdier for 166 millioner kroner, hvorav mellom 130 og 140 millioner vil være ren gevinst.

Roche-samarbeid

Den største gevinsten vil dog komme hvis Vaccibody lykkes i sitt prosjekt som går ut på å lage en vaksine som skal hjelpe pasientens immunforsvar til å gå til angrep på skader i kreft­cellene. Vaksinen kan brukes på alle kreftformer, men i første omgang er det snakk om å bruke den på lunge, føflekk- blære, nyre, og hode-halskreft.

– Selskapet har en veldig positiv utvikling på utviklingsprosjektene. Det er det ingen tvil om, sier Tom Pike.

Nylig meldte Vaccibody at de hadde inngått samarbeid med Roche om å utforske en kombinasjon av flere behandlinger hos pasienter med livmorhalskreft. Fase II-studier med opptil 50 pasienter skulle igangsettes i andre halvdel av 2019.

Pengene fra emisjonen skal brukes til disse fase II-studier med Vaccibodys neoantigen­program samt til vanlig arbeids­kapital i selskapet.

[Boms]

Det Erna skriver her så useriøst at det egentlig burde forbigås i stillhet, men om det er noen som ikke kjenner Vaccibody så godt kan det vel være greit å skrive ned et par fakta.

1. Vaccibody sin DNA terapeutiske vaksine mot livmorhalskreft VB10.16 har vist fantastisk gode resultater i fase IIa, og skal nå gå i videre tester sammen med Roche sin immune-checkpoint inihibitor. VB10.16 er en standardisert vaksine som er “enkel” å produsere og livmorhalskreft er en stor og dødelig kreft variant. Vaccibody oppgir følgende informasjon: About cervical cancer
   Cervical cancer is the most commonly occurring cancer among women in developing countries and is the second most commonly occurring cancer amongst women worldwide. An estimated 45,800 cases of cervical cancer will be diagnosed in the US and EU in 2019 and similarly an estimated 18,400 deaths from cervical cancer will occur in 2019. Cervical cancer is caused by high risk HPV. HPV16 is the type that most frequently causes cancer.
2. Den individuelle VB10.NEO vaksinen testes ut på melanom, lunge, blære, nyre og hode/hals kreft. Alle disse kreftformene gir et enormt potensiale, for dette er dessverre får vi si store og alvorlige kreftformer. Det er selvfølgelig vanskelig å vite hva produksjonskostnaden for en individualisert medisin vil bli, men i forsøkene deres har de til nå klart å produsere og levere/behandle alle pasientene med en vaksine tilpasset den enkelte pasientens tumor.

Vaccibody har hatt fokus på at deres produkter skal kunne bli en kommersiell og praktisk gjennomførbar behandling, og så langt har de levert på både effekt og resultater. Så at dette bare skal være et nisjeprodukt og bli et “jallaselskap” må argumenteres bedre for og ikke bare vise til et annet selskap vedkommende har tro på.

Se forøvrig ny pressemelding om den endelige analysen av fase IIa forsøket. http://www.vaccibody.com/news/

[Dexsign]

Positive 12-month results from phase IIa clinical study in high grade cervical dysplasia provides Proof-of-Concept for Vaccibody’s immunotherapy platform and lead candidate VB10.16.

Oslo, March 25, 2019 Vaccibody AS today announced positive 12-month results from the phase IIa part of the clinical study VB C-01. This study is a first human dose, open-label, multicenter phase I/IIa study of VB10.16 immunotherapy for the treatment of high grade Cervical Intraepithelial Neoplasia (CIN 2/3) caused by human papillomavirus 16 (HPV16). The primary objective of the study was to evaluate the safety and tolerability of VB10.16. The secondary objectives were to assess T cell mediated immune responses in the peripheral blood and to evaluate early signs of efficacy by means of CIN regression and HPV clearance. The vaccine was delivered with a PharmaJet® Stratis Needle-free Injection System.

The phase 1 part of the trial has previously been reported. It was completed in 2017 and showed that VB10.16 was well tolerated with no clinical important safety signal, the optimal vaccine schedule was identified (week 0, 3, 6) and suggested adding a fourth vaccination to maintain the strong immunogenic response.

The phase 2a study enrolled 18 CIN2/CIN3 patients, 1 patient was not HPV16 positive and thus 17 patients received four doses of 3 mg VB10.16 at week 0, 3, 6 and 16. The treatment with the four doses of VB10.16 was well tolerated. No serious adverse advents (SAEs) or unexpected adverse events were reported. The most frequently reported AEs were transient mild to moderate reactions at the injection site.

Two patients had conization and one patient withdrew after 9 months and could not be assessed at 12 months visit. Of the remaining 14 patients 12 patients showed a reduction in the lesion size; 8 had more than a 50% reduction in lesion size. Presence of HPV16 was evaluated from immunohistochemistry (p16) and COBAS (Roche diagnostics), all patients had positive HPV16 at study entry and 8 of the 14 patients had negative HPV16 in one or both of the two tests at 12 months, indicating clearance of the HPV16 infection. Histopathological regression to low grade neoplasia (CIN1) or no disease was seen in 8 patients. Of the 6 patients that has not regressed to CIN1 or less at 12 months, 5 patients showed upregulation of PD-L1 in the lesions which may delay or inhibit elimination of all affected cells. Three of these patients had also persistent co-infection with other high-risk HPV strains, including one patient which had cleared HPV16.

Immunological analyses of the peripheral T cell responses demonstrated a strong HPV16-specific T cell immune response in 17 of 17 patients. The response was increased after vaccination in 16 of 17 patients against both HPV16 E6 and E7 antigens used in the vaccine. One patient had a strong baseline response and the response was not further increased.

These results constitute a proof-of-concept for VB10.16 and the Vaccibody DNA vaccine technology delivered by jet injection to induce rapid, strong and long-lasting immune responses which can lead to elimination of pre-malignant and malignant cells. Interestingly, the observed PD-L1 upregulation provides a strong rationale for moving VB10.16 into HPV16 positive cancer in combination with anti- PD-1/PD-L1 checkpoint inhibitor therapy.

Martin Bonde, CEO of Vaccibody, commented: We are very pleased with the 12-months results from the phase IIa clinical study in high grade cervical dysplasia. The data support what we have reported earlier and delivers a solid clinical proof-of-concept for Vaccibody’s immunotherapy platform and lead

candidate VB10.16. The fact that we observe PD-L1 upregulation in response to vaccination in the patients that do not have CIN regression at 12 months, substantiates the mechanism of action of the vaccine and invites to pursue potential synergistic effects by combining therapeutic Vaccibody cancer vaccines and checkpoint inhibitors, like we have observed in preclinical experiments. We are therefore very excited about our newly entered collaboration with Roche to explore a combination of Vaccibody’sVB10.16 and the PD-L1-blocking immune-checkpoint inhibitor atezolizumab (Tecentriq®) in patients with advanced cervical cancer. Based on the above data Vaccibody plans to start a phase II study with up to 50 cervical cancer patients in the second half of 2019.

About cervical cancer

Cervical cancer is the most commonly occurring cancer among women in developing countries and is the second most commonly occurring cancer amongst women worldwide. An estimated 45,800 cases of cervical cancer will be diagnosed in the US and EU in 2019 and similarly an estimated 18,400 deaths from cervical cancer will occur in 2019. Cervical cancer is caused by high risk HPV. HPV16 is the type that most frequently causes cancer. It has been reported to be the most common genotype in high grade cervical intraepithelial neoplasia. It is detected in up to 60% of all cervical cancers, especially in younger women and it has also been found to play an essential role in the development of several other cancer types (approximately 90% of anal cancers; 40% of penile, vaginal, and vulvar cancers; 25% of oral cavity cancers and 35% of oropharyngeal cancers). Gardasil® and Cervarix® are preventive HPV vaccines which prevent infection of HPV, but these do not have an effect in already infected patients. A high percentage of the eligible population for the preventive vaccines does not get vaccinated, thus HPV infection and HPV+ cancer still requires effective therapeutic interventions. There is currently no available therapy treating HPV specifically.

About Vaccibody

Vaccibody is a clinical-stage biopharmaceutical company dedicated to the discovery and development of novel immunotherapies. The company is one of the leaders in the rapidly developing field of individualized cancer neoantigen vaccines and is using the Vaccibody technology to generate best-in-class therapeutics to treat cancers with a high unmet medical need. A phase I/IIa neoantigen clinical trial is currently enrolling patients with locally advanced or metastatic melanoma, non-small cell lung carcinoma, clear renal cell carcinoma as well as urothelial or squamous cell carcinoma of the head and neck. Vaccibody’s most advanced program (VB10.16) is a therapeutic DNA vaccine against HPV16 induced pre-malignancies and malignancies. Further information about the company and its drug development programs and capabilities may be found online at http://www.vaccibody.com

Contact:

Martin Bonde CEO

+45 2025 3560

mbonde@vaccibody.com

Vaccibody AS

Oslo Research Park Gaustadalléen 21 0349 Oslo, Norway

[Investor]

Vaccibody AS and Nektar Therapeutics Present New Preclinical Data from their Immuno-Oncology Collaboration at the American Association for Cancer Research (AACR) Annual Meeting 2019
Oslo/San Francisco, April 1, 2019 – Vaccibody AS and Nektar Therapeutics (Nasdaq: NKTR) today announced presentation of new preclinical data for VB10.NEO, a personalized neoantigen cancer vaccine, combined with bempegaldesleukin (NKTR-214 or bempeg), a CD122-preferential IL-2 pathway agonist. These data were presented today in a poster session at the American Association for Cancer Research (AACR) Annual Meeting 2019.
"We are excited to present these novel preclinical data that show combining bempeg with VB10.NEO synergize to increase both the breadth and the depth of the neoantigen-specific immune response. These unique and non-overlapping mechanisms produced an expansion of the VB10.NEO elicited neoantigen-specific T cells and demonstrated enhanced anti-tumor efficacy in mice. We look forward to evaluating this novel immuno-oncology combination in a clinical study in patients with advanced or metastatic squamous cell carcinoma of head and neck later this year,” said Agnete B. Fredriksen, Ph.D., Vaccibody’s President and Chief Scientific Officer.
VB10.NEO is designed to specifically activate a patient’s immune system to tumor-specific antigens, called neoantigens. Bempeg is designed to expand and proliferate tumor antigen-specific T cells in the tumor microenvironment. Addition of bempeg to VB10.NEO is intended to drive maximal expansion of vaccine-induced neoantigen-specific T cells for the treatment of cancer.
“Personalized T cell vaccines could play a critical and central role in cancer immunotherapy. These preclinical data highlight the potential of combining a personalized cancer vaccine with a T cell proliferator to induce maximal expansion of vaccine-induced T cell clones and durable responses and specific anti-tumor immunity,” said Jonathan Zalevsky, Ph.D., Chief Scientific Officer at Nektar. “We are highly encouraged by these results and look forward to testing this unique approach to personalized cancer treatment in patients with squamous cell carcinoma of the head and neck.”
Details of the poster presentation at AACR are as follows and will be available for download at the time of presentation at http://www.vaccibody.com/scientific-presentations/ and https://www.nektar.com/download_file/662/0.
Abstract #

[Investor]

[Boms]

Dette ser utrolig spennende ut, se klipp fra posteren under.
Økningen i respons for både CD8 og CD4 øker jo fantastisk mye bedre når VB10.NEO og NKTR-214 kombineres. Så får vi håpe at effekten på mennesker kan bli like bra som for disse heldige små hvite musene.

[Boms]

Den nye biotech analytikeren i Arctic, Pål Falck, har lagt ut en kort presentasjon av Vaccibody som kanskje kan være interessant som en kort innføring/oppdatering på selskapet for de som ikke har fulgt det tidligere.

Etter hva jeg har hørt har det blitt omsatt ca 150’ aksjer på 44,- de siste to ukene.

[Investor]

VACCIBODY ANNOUNCES STRONG NEOANTIGEN-SPECIFIC T CELL RESPONSES
INDUCED IN CANCER PATIENTS WITH LOW MUTATIONAL BURDEN AFTER VB10.NEO
VACCINATION.
Oslo, June 26, 2019 Vaccibody AS today announced strong immunogenicity data from the
neoantigen cancer vaccine clinical trial VB N-01. Immunogenicity was assessed in two patients
with renal cell carcinoma (RCC) and two patients with squamous cell carcinoma of the head and
neck (SCCHN) after treatment with a VB10.NEO in combination with checkpoint inhibitor
therapy as per protocol. Before VB10.NEO vaccination, these patients had been treated with the
checkpoint inhibitor nivolumab for 12-32 months with stable disease as best response. One
patient was progressing at start of vaccination. All patients had low tumour mutational burden
ranging from 1.7-3.2 mutations/Mb. The top 20 neoepitopes predicted by Vaccibody’s
proprietary NeoSELECTTM algorithm was selected for each of the fully personalized VB10.NEO
neoantigen vaccines. Immunogenicity to each individual neoepitope has so far been assessed
after 3 to 6 vaccinations of VB10.NEO by an in vitro stimulated IFN-γ ELISpot. Strong T cell
responses were observed in all these first four patients tested. T cell responses were
significantly increased in post-vaccination samples towards 63% of the neoepitopes. The
response to the vaccine was very solid with an average increase of more than 1200 SFU per
million PBMC which is on average a 250-fold increase from baseline. The breadth and the
strength increased with number of vaccinations. An amplification of existing neoepitope-specific
T cells as well as de novo responses were observed in all patients.
Agnete Fredriksen President and CSO of Vaccibody, commented: We are very pleased to see the
strong T cell responses observed in all of the first four patients at the initial assessments. We are
excited to see that the vaccine was able to induce so strong T cell responses even in the patients
with a history of many lines of previous treatment and no objective response to long-term
treatment with anti-PD-1. All these first patients had low tumour mutational burden (TMB)
leaving the number of mutations limited for selection of immunogenic neoepitopes, hence we
believe the high percentage of the neoantigen-specific immune responses observed
substantiates Vaccibody’s unique neoepitope prediction method and delivery mechanism. We
are very intrigued by the de novo responses induced by the vaccine. The baseline responses and
hence the number of de novo responses were surprisingly different between the patients
assessed so far and we are looking forward to characterizing the T cells in more detail and follow
the clinical responses in these patients.

[Boms]

En relativt liten populasjon?
De tester nå i indikasjonene:

1. Melanoma
2. NSCLC
3. RCC
4. Urothelial
5. SCCHN

Meget kostbart produkt?

Så i mine øyne er dette verken små indikasjoner eller en veldig dyr medisin å produsere.

Og når det gjelder sannsynlighet for godkjennelse så er det vel alt for mange selskap hvor investorene overvurderer sjansen for suksess.

[Boms]

Har bare tall fra 2 kvartalsrapporten sammenlignet med 1. kvartal:

[Investor]

Vaccibody AS, a clinical stage company focused on developing personalized neoepitope cancer vaccines to target solid tumors, will host its capital markets day on November 12 and is pleased to invite investors, analysts and press to presentations by the members of the company’s executive management team and by Ulrich Granzer, PhD, founder of Granzer Regulatory Consulting & Services. Dr. Granzer has a wide range of experience in all aspects of drug development and regulatory affairs, with particular focus on bringing novel therapies to market.

Venue: Forskningsparken, Gaustadalléen 21, 0349 Oslo. Meeting room Faros.

Date: Tuesday, 12th November 2019

Agenda:

14.00-14.10	Introduction	Michael Engsig
14.10-15.00	Update on the VB N-01 study including the clinical data	Agnete Fredriksen
15.00-15.45	Status of the cancer vaccine field and development of novel immunotherapies	Ulrich Granzer
15.45-16.05	Company update	Michael Engsig
16.05-16.30	Questions & Answers	All
16.30-17.30	Mingling, snacks and drinks	All

[Investor]

Kursøkningen siste måneder kom kanskje ikke tilfeldig?

Dette må sies å være breaking news, fantastisk sterke resultater fra Vaccibody!

1
PRESS RELEASE
VACCIBODY ANNOUNCES INITIAL POSITIVE CLINICAL RESPONSES IN PATIENTS WITH LOCALLY ADVANCED OR METASTATIC CANCER TREATED WITH VB10.NEO NEOANTIGEN CANCER VACCINE
VB10.NEO is the first neoantigen cancer vaccine to demonstrate induction of strong cancer-specific immune responses which leads to clinical responses in several patients with locally advanced or metastatic disease.
Interim results from phase I/IIa clinical trial suggests a clear link between selection of high-quality neoepitopes, generation of strong neoepitope-specific CD8+ T cell responses and clinical responses.
Poster detailing these results to be presented at the Society for Immunotherapy of Cancer (SITC) Annual Meeting held in Maryland, USA, 9 November 2019
Oslo, November 5, 2019 Vaccibody AS, a clinical-stage biopharmaceutical company dedicated to the discovery and development of novel cancer vaccines, today announces strong preliminary data from the ongoing VB N-01 phase I/IIa clinical trial of the VB10.NEO neoantigen cancer vaccine. The data is from the first 16 patients assessed for safety after treatment with a VB10.NEO, and the first 14 patients assessed for clinical responses.
Key highlights include:
• Clinical responses were observed after treatment start with VB10.NEO in 50% of all analysed patients across tumour types
o Lesion size reductions of 10-100% or stabilization of prior progressing lesions.
o All four head and neck cancer (SCCHN) patients, the melanoma patient, the non-small cell lung cancer (NSCLC) patient and one of eight renal cancer (RCC) patients show a clinical response after starting VB10.NEO vaccinations.
• Clinical responses correlate with high quality neoepitopes and strong de novo CD8 positive neoepitope-specific T cell responses induced by VB10.NEO.
2
Prof. Dr. med. Jürgen Krauss, of the Department of Medical Oncology, National Center for
Tumor Diseases, University Hospital Heidelberg, Germany, and coordinating investigator of
the study, said:
"I am very pleased with the progress of this clinical phase I/IIa for Vaccibody’s neoantigen cancer
vaccine. The data indicate that VB10.NEO induces best in class neoepitope-specific immune
responses and the clinical responses observed in the first patients are highly intriguing. Since we
have not observed any safety concerns with this treatment so far, there is a very high interest to
broaden the patient population exposed to this innovative treatment. We are highly committed
to continue this exciting program and we hope this clinical trial will help pave the way for a novel
class of new efficacious and safe treatment for cancer patients.”
Agnete Fredriksen President and CSO of Vaccibody, commented:
“We are very excited to see a clinical response with a clear effect on both the size and the
growth of the lesions in a high number of the first patients treated with VB10.NEO as early as 9
weeks after the first dose of VB10.NEO.
Since we enrolled patients that had been treated with checkpoint inhibitor therapies for at least
5 months before the first dose of VB10.NEO, we are confident that in the cases of actual
reductions of lesion sizes this effect can be attributed to the vaccine since most responses to
checkpoint inhibitors happens within the first 3-5 months. After this period, further reductions in
lesions size are unexpected and lesions that progress usually continue to grow without further
interventions. Also, the observation of a strong correlation between high quality neoepitopes in
the vaccine and the strength of de novo CD8 neoepitope-specific immune responses that
translate into clinical responses is very encouraging. Importantly, this confirms the ability of
Vaccibody’s vaccine delivery platform to generate strong CD8 T cell responses, critical for tumour
killing.
Importantly, responses were also observed in patients with low tumour mutational burden that
progressed after long-term checkpoint inhibitor therapy.”
Michael Engsig, CEO of Vaccibody, continued:
“To our knowledge, this is the first time that a neoepitope cancer vaccine shows the ability to
actually shrink tumours, even in heavily pre-treated patients with advanced or metastatic
disease.
Taken together, we are very encouraged to build on these findings and continue development of
our neoantigen cancer vaccine program.”
Results
Before VB10.NEO vaccination, most patients had received multiple lines of prior anti-cancer
therapy and had been treated with a checkpoint inhibitor (CPI) (nivolumab or pembrolizumab)
for 5-32 months. All had stable disease or mixed progressive disease when enrolled into the
study. Five patients were progressing between enrolment and first dose of VB10.NEO and one
had a partial response, while the remaining patients were stable. Twelve of the 14 patients
3
continued treatment with a CPI during VB10.NEO treatment. A clinical response, defined as
either >10% reduction in the target lesions (as identified at screening) or converting progressive
lesions into stable lesions (<20% increase, up to 37 weeks follow-up) after starting VB10.NEO
treatment, was observed in seven of the 14 patients (4 SCCHN, 1 melanoma, 1 NSCLC and 1
RCC). The strongest clinical responses were most often seen in the lesions that were used to
select the neoepitopes.
Eleven patients had low tumour mutational burden (TMB), two patients had medium TMB and
one patient had high TMB. The top 20 neoepitopes predicted by Vaccibody’s proprietary
NeoSELECTTM algorithm were selected for each of the fully personalized VB10.NEO neoantigen
vaccines. Vaccibody’s proprietary DNA vaccine manufacturing process has so far yielded 100%
manufacturing success with the top 20 selected neoepitopes for all patients.
One RCC patient who discontinued CPI and started immunosuppressive treatment prior to first
dose of VB10.NEO was not included in the immunogenicity analyses. Immunogenicity to each
individual neoepitope was assessed in eight patients after six vaccinations by in vitro prestimulated
IFN-γ ELISpot. The breadth and the strength of neoepitope-specific T cell responses
were increased with number of vaccinations. Patients showing a clinical response also had the
strongest immune responses and the highest frequency of high quality neoepitopes.
The safety data for the 16 patients who has received at least one dose of VB10.NEO shows that
VB10.NEO is well tolerated. Most common adverse events attributable to the VB10.NEO
treatment were injection-related hypertensive episodes and injection site reactions.
Four patients with SCCHN were assessed, three with low TMB and one with medium TMB. Two
patients had progressive disease, one had stable disease and one had partial response at start
of VB10.NEO vaccination. The patients had been on CPI for 12-32 months before starting
VB10.NEO treatment. Strong neoantigen-specific T cell responses were seen in the vast majority
(60-90%) of the selected neoepitopes after VB10.NEO vaccination with up to 1000-fold increase.
A clinical response was observed in all four SCCHN patients: In the patients who had progressed
on CPI before starting VB10.NEO a stabilisation or reduction in the size of the target lesions
were observed after starting VB10.NEO treatment. In patients with stable disease or partial
response on CPI, a reduction in lesion size was observed after starting VB10.NEO treatment. If
the patients had multiple target lesions, the strongest response was observed in the lesions
used to select neoantigens for the vaccine. Eradication of tumour cells containing the mutations
targeted by the vaccine was observed in a follow-up biopsy from one of the patients.
One melanoma patient was assessed. The patient had high TMB and stable disease at start of
VB10.NEO vaccination and the patient had been on CPI for 10 months before treatment with
VB10.NEO vaccination. An increased neoantigen-specific T cell response was seen to 50% of the
selected neoepitopes after VB10.NEO vaccination with the majority being de novo responses. A
clinical response with lesion size reduction was observed in the patient.
4
One NSCLC patient was assessed. The patient had medium TMB and stable disease as best
response during nine months of CPI treatment before start of vaccination. Disease progression
was observed during vaccine manufacturing with the occurrence of a new lesion. A clinical
response in the form of rapid reduction in the target lesion was observed nine weeks after the
first VB10.NEO vaccination.
Eight patients with RCC were assessed for clinical response, all with low TMB. Two patients had
progressive disease and six had stable disease at start of VB10.NEO vaccination. One patient
was taken off CPI and started immunosuppressive therapy prior to the first dose of VB10.NEO.
Limited clinical responses have been observed until data-cut off (up to 37 weeks after first
VB10.NEO vaccination). Interestingly, only one of the RCC patients has had an increase of >20%
in the sum of target lesions and none of the lesions used to select neoantigens for the vaccine
has progressed (defined as >20% increase in size.) Correlating with the limited clinical
responses, fewer high-quality epitopes and neoepitope-specific immune responses were
observed.
The Poster
The Poster (ID: P424) will be presented at the Society for Immunotherapy of Cancer (SITC)
Annual Meeting Saturday, 9 November, 7:00 am - 8:30 pm local time in National Harbor,
Maryland. Vaccibody staff will be available during the poster session at SITC.
About Vaccibody
Vaccibody is a clinical-stage biopharmaceutical company dedicated to the discovery and
development of novel immunotherapies. The company is a leader in the rapidly developing field
of individualized cancer neoantigen vaccines and is using the Vaccibody technology to generate
best-in-class therapeutics to treat cancers with a high unmet medical need. A phase I/IIa
neoantigen clinical trial is now enrolling patients with locally advanced or metastatic melanoma,
non-small cell lung carcinoma, clear renal cell carcinoma as well as urothelial or squamous cell
carcinoma of head and neck. Vaccibody has a collaboration with Nektar Therapeutics, planning
to start testing VB10.NEO in combination with bempegaldesleukin (NKTR-214) in squamous cell
carcinoma of head and neck in H2 2019. Vaccibody’s most advanced program (VB10.16) is a
therapeutic DNA vaccine against HPV16 induced pre-malignancies and malignancies. The firstin-
human study (phase I/IIa), evaluating the safety and immunogenicity of VB10.16 in women
with high grade cervical intraepithelial neoplasia (HSIL; CIN 2/3) has been finalized and has
published positive 12 months data. Vaccibody has recently started a collaboration with Roche,
exploring VB10.16 in combination with CPI atezolizumab (Tecentriq™) in up to 50 patients with
advanced or recurrent cervical cancer. First patient is expected to be vaccinated in H1
2020. Further information about the company and its drug development programs and
capabilities may be found online at http://www.vaccibody.com
About VB10.NEO
VB10.NEO, is Vaccibody’s proprietary therapeutic DNA vaccine which uses the patient’s own
neoantigens for the personalized treatment of cancer patients. A phase I/IIa neoantigen clinical
trial is currently enrolling patients with locally advanced or metastatic melanoma, non-small cell
5
lung carcinoma, clear renal cell carcinoma as well as urothelial cancer or squamous cell
carcinoma of the head and neck.
About VB N-01
VB N-01 (DIRECT-01) is an open-label phase 1/2a study, designed to evaluate the safety,
immunogenicity and efficacy of administrating personalized VB10.NEO in combination with
checkpoint blockade in patients with locally advanced or metastatic solid tumors including
melanoma, NSCLC, renal cell carcinoma, urothelial cancer or head and neck cancer, who have
not achieved a complete response by at least week 12 on checkpoint blockade as respective
standard of care (NCT03548467).
Contact:
CEO Michael Engsig
Vaccibody AS
Cell: +45 6173 1509
mengsig@vaccibody.com
President and CSO Agnete Fredriksen
Cell: +47 99634215
abfredriksen@vaccibody.com
Vaccibody AS
Oslo Research Park
Gaustadalléen 21
0349 Oslo, Norway

[Investor]

Her er resultatene fra dagens melding oppsummert. Merk at disse resultatene ble oppnådd blant pasienter som har gått på dagens state of the art behandling, sjekkpunkthemmere (PD-L1-hemmere), Keytruda og Opdivo. Disse er mega blockbustere som selger for milliarder av dollar. Legg merke til at flere har gått på denne behandlingen i månedsvis og kun 1 av de 14 hadde PR(partial response). Vaccibody klarer altså å få det de kaller for “Clinical Response” i halvparten av disse pasientene. Clinical Response er her definert som følger:

A clinical response, defined as
either >10% reduction in the target lesions (as identified at screening) or converting progressive
lesions into stable lesions (<20% increase, up to 37 weeks follow-up) after starting VB10.NEO
treatment,

Man skal kanskje være forsiktig med å konkludere da det bare er 14 pasienter, men dette er oppsiktsvekkende resultater som vil bli lagt merke til hos Big Pharma, feks Merck, som selger Keytruda og BMS som selger Opdivo. Kan Vaccibody her ha laget noe som fungerer bedre enn disse blockbusterne? SITC konferansen blir veldig interessant. Jeg håper vi da får data på pasientnivå og klassifisering iht RECIST, feks antall CR, PR, SD osv.

Resultatene oppsummert:

Keytruda og Opdivo solgte for tilsammen over 15 mrd dollar i 2018. Ikke rart at Vaccibody økte sin markedsverdi med 1 mrd kroner idag.

[Investor]

Som en referanse til Vaccibodys resultater kan vi se på selskapet NextCure som utvikler behandling for lungekreftpasienter som ikke responderer på CPI. Dette er en meget god referanse, ettersom Vaccibody også behandler pasienter som ikke responderer på CPI.

Så hva slags resultater rapporterte Nextcure?

In the Phase I dose-escalation portion of an open-label Phase I/II trial, NC318 showed a best observed response rate of 27% among seven non-small cell lung cancer (NSCLC) patients, including one complete response (CR) and one partial response (PR). The CR was ongoing at 41 weeks. The disease-control rate (DCR) in the NSCLC cohort was 71%.

For å sette dette i perspektiv kan vi vise til Hva ledende CPI’er har oppnådd:

The NC318 results, however, are similar to Phase I data for the PD-1 and PD-L1 inhibitors. For example, at the American Society of Clinical Oncology (ASCO) meeting in 2014, Merck & Co. Inc. (NYSE:MRK) presented Phase Ib data for its now blockbuster Keytruda pembrolizumab, which had an ORR of 9-33% in NSCLC patients and a DCR of 40-70%, while Bristol-Myers Squibb Co. (NYSE:BMY) reported Phase Ib data for Opdivo nivolumab, which had an ORR of 22-50% and a DCR of 24-45% (see “Advantage Merck”).

Så til poenget:

Vi har til gode å se respons hos Vaccibodys pasienter iht RECIST-klassifisering, men det kommer forhåpentlig i helga.
Men - vi vet at flere pasienter hadde reduksjon i tumorstørrelse (fra 10%-100%). Kan jo ikke leses på annen måte enn at også Vaccibody hadde 1 eller flere CR?
Blir uhyre interessant å få høre om hva slags ORR de fikk.

For NextCures del betydde disse resultatet at selskapsverdien økte med hele 1,2 mrd USD! Smak på den -10 mrd kroner!

Så hva er en fornuftig økning i MCAP i Vaccibody? SÅ langt har kursen økt fra 61 til 85, som utgjør en økning i Market Cap på ca 1,3 mrd, altså bare en brøkdel av hva Nextcure økte med…

Så kanskje er kursøkningen vi har sett bare den spede begynnelsen. Som et unotert selskap i et land som ikke har noen tradisjon for biotech tar det nok noe tid før denne perlen oppdages, særlig internasjonalt. Kanskje blir SITC en arena for dem å vise seg fram. Blir interessant å se om investorer oppdager aksjen før Big Pharma oppdager dem.

Kilder:

NextCure’s NC318 data shines light on SIGLEC15 as next hot IO target

[Investor]

Noen inntrykk fra dagens kapitalmarkedsdag i Vaccibody:

• Voldsomt trøkk, vil anta ca 100 personer tilstede

• Utrolig flott gjennomgang av Agnete Fredriksen på de ferske kliniske dataene. Bidro iallfall til at jeg fikk en dypere forståelse av dataene og hvor gode de faktisk er. De har lagt veldig mye jobb ned i designet av studie for å kunne være sikre på at de responser de ser skyldes deres vaksine og ikke CPI. De viste blant annet en slide som viste typiske responser på CPI, hvor responsene skjer de første 4-6 måneder for deretter å flate ut. Det er veldig uvanlig å se responser 12-32 mnd etter start på CPI, slik som er tilfellet med pasientene Vaccibody har behandlet.

• Synes det var interessant at de viste at de fikk inn mange pasienter med såkalt lav tumormutasjonsbyrde. Disse er det vanskeligere å få respons hos, fordi immunsystemet har vanskeligheter med å kjenne igjen disse kreftcellene. Pasientene de har fått inn i sin studie er dermed blant de mest krevende å få respons hos, noe som styrker dataene ytterligere.

• Presentasjonen til Ulrich Ganzer, som rådgiver biotech og pharmaselskaper i møte med myndigheter (500 selskaper på kundelisten) var også interessant, særlig når han kunngjorde at dette var "strongest data I have ever seen"! Smak på den! I Q&A-runden fikk han spørsmål om han kunne sammenlikne BioNTech og Vaccibody. Etter å ha snakket litt generelt om BioNTech, som han tydeligvis kjente godt(som et tysk selskap), konkluderte han med at Vaccibody har bedre data enn BioNTech. Mcap BioNTech er i skrivende stund 4 milliarder dollar…

• Ganzer mente at Vaccibody kunne komme på markedet allerede om 2 år hvis dataene fortsetter å være så sterke. Han sammenliknet Vaccibodys vaksine med CAR-T (bla Kymriah), i og med at den også er persontilpasset. Forskjellen er at CAR-T er en medisin med høy risiko, ting kan gå galt (eksempel som ble nevnt er at immunsystemet kan gå til angrep på celler i hjerte, med rask død som konsekvens). Vaccibodys vaksine derimot har en svært god sikkerhetsprofil.

• Ganzer er ekspert på å rådgi selskaper i møte med regulatoriske myndigheter. Han sier at myndighetene nå jobber med å tilpasse seg den nye persontilpassede medisinen. Randomiserte studier er i praksis ikke mulig fordi du ikke får to sammenliknbare populasjoner. Fordelen er mindre studier, ulempen er at du må bevise større klinisk effekt. Vanlig forskjell som kreves i randomiserte studier er ca 2 mnd økt overlevelse, mens man ved single-arm studier trenger større klinisk effekt.

• Snakket med analytiker Pål Falck i etterkant og han sier han kommer med en analyse på selskapet snart. De har per tid ikke dekning såvidt jeg vet.

Dette var bare et utdrag fra det jeg husker, tok ikke notater, burde gjort det. Håper selskapet legger ut presentasjonene så kan folk se selv. Håper andre som var der kan legge til det jeg glemte.

[Boms]

@safin Det er vel meningen at et forum skal være et forum for meningsutvekslinger og nyheter, så du kan jo vurdere om du selv burde grave litt etter nyheter og informasjon

Selskapet skrev selv i siste kvartalsrapport følgende:

Outlook
For the upcoming twelve months, the Company’s plans include:
• Clinical Trial for cancer neoantigen vaccine (VB10.NEO)
o Continue enrolment of the clinical phase I trial of patients with locally advanced or
metastatic melanoma, non-small cell lung carcinoma, clear renal cell carcinoma,
urothelial cancer or squamous cell carcinoma of the head and neck.
o Interim report on safety, immunogenicity and early signs of efficacy. (Post Quarter
Note: This was released in November.)
• Nektar collaboration
o Initiation of the clinical trial evaluating the combination of VB10.NEO and NKTR-214
and first patient dosed.
• Clinical Trial in cervical cancer combining VB10.16 and checkpoint inhibitor atezolizumab
in collaboration with Roche
o Submission of the clinical trial application (Ph IIa) to the relevant regulatory bodies.
o Initiation of the clinical trial evaluating the combination of VB10.16 and atezolizumab
and first patient dosed.

---

Fra EU databasen vet man at kombostudien med Roche er godkjent for rekruttering så der kommer nok FPD (first-patient-dosed) melding anytime.
I tillegg er kombinasjonsarmen med NKTR-214 og VB10.NEO godkjent og klar for rekruttering den også, men der tar det jo tid fra biopsi til pasienten får første dose så jeg forventer nyheten der i februar/mars.

[Savepig]

Nektar Therapeutics (NektarNews)

[oslokay]

VACCIBODY FINALIZES PATIENT ENROLMENT IN VB N-01 PHASE I/IIa TRIAL WITH ITS
NOVEL VB10.NEO NEOANTIGEN CANCER VACCINE

• Vaccibody has reached the enrolment target of 50 patients in its VB N-01 basket trial
for a variety of cancer types with high unmet medical need
• Patients have been recruited into all six arms of the basket trial, thereby optimizing the
read-outs on efficacy and safety

Oslo, Norway, August 21, 2020 – Vaccibody AS, a clinical-stage biopharmaceutical company
dedicated to the discovery and development of unique immunotherapies, today announced
that it has reached the enrolment target of 50 patients and that it has finalized recruitment of
patients to all study arms of its ongoing VB N-01 phase I/IIa clinical trial of the personalized
VB10.NEO neoantigen cancer vaccine.

Michael Engsig, CEO of Vaccibody, said: “VB10.NEO is a groundbreaking approach to
personalized cancer treatments and has a large commercial potential. We are thus very
excited to have reached this important milestone for the VB N-01 trial. The initial clinical
results presented at SITC in November 2019 were very encouraging and we will communicate
the next steps in the development of VB10.NEO in Q4 2020.”

VB N-01 is a basket trial for patients with locally advanced or metastatic melanoma, non-small
cell lung carcinoma, clear renal cell carcinoma as well as urothelial cancer or squamous cell
carcinoma of the head and neck. In the trial the safety, feasibility and efficacy of treatment
with the personalized VB10.NEO vaccine is evaluated, including one study arm evaluating the
combination of VB10.NEO and bempegaldesleukin (NKTR-214) in patients with head and neck
cancer. The trial has been recruiting patients from seven clinical sites in Germany.

Siri Torhaug, Chief Medical Officer of Vaccibody adds, “We are truly grateful to the patients
for participating in the trial, to our investigators at the clinical trial sites, our supply chain
partners and the dedicated Vaccibody team who has done a great job by finalizing the
enrolment and ensuring successful manufacture of the patient specific VB10.NEO products
despite the challenging COVID-19 situation. Further, we are pleased that the recruitment of
patients distributes well across all of the six treatment arms.”

[Boms]

Professor Bjarne Bogen som er en av medoppfinnerne til Vaccibody sin teknologi får i dag en innovasjonspris fra UiO, I artikkelen under står det interessant nok følgende:
– Det blir spennende å se resultatene av studier hvor vaksineprinsippet anvendes på kreftpasienter. Et fase 1-studium hvor vaksineprinsippet benyttes som en influensavaksine er også på trappene på OUS, her er det forskere ved Klinmed som står bak. Vaksineprinsippet kan også kanskje brukes til å utvikle en vaksine mot COVID-19 virus, og spede forsøk er i gang, forteller Bogen.

UiOs Innovasjonspris til Bjarne Bogen - Institutt for klinisk medisin