BergenBio Fundamentale Forhold (BGBIO)

Logdec · april 2, 2020, 1:21am

Part 5 Bergenbio Patent søknader

Under finner dere søknader som er under vurdering. De kan kommer når som helst.
Merknad: det kan ta mellom 2 -5 år før en patent blir innvilget.

https://patents.justia.com/patent/20200072839 Publication date: March 5, 2020
https://patents.justia.com/patent/20200010421 Publication date: January 9, 2020
https://patents.justia.com/patent/20190177419 Publication date: June 13, 2019
https://patents.justia.com/patent/20180371096 Publication date: December 27, 2018
https://patents.justia.com/patent/20180208989 Publication date: July 26, 2018
https://patents.justia.com/patent/20180153888 Publication date: June 7, 2018
https://patents.justia.com/patent/20170314077 Publication date: November 2, 2017

Her finner dere litt mer om hver av patentsøknadene.

METHOD
https://patents.justia.com/patent/20200072839
Filed: May 10, 2019
Publication number: 20200072839 @ Publication date: March 5, 2020
Type: Application
Inventors : Jim Lorens (Bergen), Crina Tiron (Bergen)

The use of Akt3 as a biomarker for detecting the occurrence of epithelial-to-mesenchymal transition (EMT) in a subject, and the use of Akt3 inhibitors to treat cancer is disclosed herein. Also disclosed are various methods for detecting the occurrence of epithelial-to-mesenchymal transition (EMT) in a subject by measuring Akt3 expression and/or activity.

Pharmaceutically Active Compounds
https://patents.justia.com/patent/20200010421
Type: Application
Filed: May 15, 2019
Publication number: 20200010421 @ Publication date: January 9, 2020
Inventors: Jason John Shiers, John Paul Watts, Stuart Thomas Onions, Mohammed Abdul Quddus, Joseph William Wrigglesworth, Colin Peter Sambrook-Smith, Alan Naylor, Derek Londesbrough

The invention is directed to compounds of general formula (I) and pharmaceutical compositions containing such compounds. The compounds and compositions have valuable pharmaceutical properties. In particular, they may be used for the treatment of cancer. Novel intermediates and novel methods of preparation are also disclosed.

ANTI-AXL ANTAGONISTIC ANTIBODIES
https://patents.justia.com/patent/20190177419
Filed: December 19, 2018
Publication number: 20190177419 @ Publication date: June 13, 2019
Type: Application
Inventors: David Robert MICKLEM, Sergej KIPRIJANOV, James Bradley LORENS, Lavina AHMED, Linn Hodneland NILSSON, Tone SANDAL

Described are antibodies that specifically bind to the Axl protein and inhibit the interaction between Axl and the Axl-ligand, Gas6. Also disclosed are methods for the production and use of the anti-Axl antibodies.

ANTI-AXL ANTIBODIES
https://patents.justia.com/patent/20180371096
Filed : Apr 20, 2018
Type: Application
Publication number: 20180371096 @ Publication date: December 27, 2018
Inventors : David Robert MICKLEM (Bergen), Sergej KIPRIJANOV (Oslo), Linn Hodneland NILSSON (Bergen), Lavina AHMED (Bergen), Hallvard HAUGEN (Bergen)

This application is a continuation of U.S. application Ser. No. 15/318,028, filed Dec. 12, 2016, which is a national phase entry pursuant to 35 U.S.C. § 371 of International Application No. PCT/EP2015/063700, filed Jun. 18, 2015, which claims the benefit of priority of Great Britain Application No. 1410826.0, filed Jun. 18, 2014, each of which is incorporated by reference herein in its entirety for any purpose. The present disclosure relates to antibodies which specifically bind to the Axl protein. Also disclosed are methods for the production and use of the anti-Axl antibodies.

BIOMARKERS FOR CANCER
https://patents.justia.com/patent/20180208989
Filed: July 8, 2016
Publication number: 20180208989 @ Publication date: July 26, 2018
Type: Application
Inventors: Monica HELLESOY, Linn Hodneland NILSSON, David Robert MICKLEM

The use of PHGDH as a biomarker for detecting the occurrence of epithelial-to-mesenchymal transition (EMT) in a subject, and the use of PHGDH modulators to treat cancer is disclosed herein. Also disclosed are various methods for detecting the occurrence of epithelial-to-mesenchymal transition (EMT) in a subject by measuring PHGDH expression and/or activity.

COMBINATION THERAPY WITH AXL INHIBITOR AND IMMUNE CHECKPOINT MODULATOR OR ONCOLYTIC VIRUS
https://patents.justia.com/patent/20180153888
Type: Application
Filed: May 27, 2016
Publication number: 20180153888 @ Publication date: June 7, 2018
Inventors: James Bradley LORENS, Gro GAUSDAL

An Axl inhibitor and one or more immune checkpoint (activity) modulators and/or one or more oncolytic viruses, for use in the prevention, treatment or management of cancer, wherein the Axl inhibitor and the one or more immune checkpoint (activity) modulators and/or the one or more oncolytic viruses are administered concurrently, separately or sequentially; compositions containing such components in combination; and methods of treating cancer in a patient by administering such components in combination.

SLFN11 AS BIOMARKER FOR AML
https://patents.justia.com/patent/20170314077
Filed: November 13, 2015
Publication number: 20170314077 @ Publication date: November 2, 2017
Type: Application
Inventors : David Robert MICKLEM (Bergen), Monica HELLESOY (Bergen), Linn Hodneland NILSSON (Bergen)

The use of Slfn11 as a biomarker for detecting the occurrence of epithlial-to-mesenchymal transition (EMT) in a subject, and the use of Slfn11 modulators to treat cancer is disclosed herein. Also disclosed are various methods for detecting the occurrence of epithelial-to-mesenchymal transition (EMT) in a subject by measuring Slfn11 expression and/or activity.

Logdec · april 2, 2020, 1:22am

Part 6 In the Shoes of Investors

After information technology, biotechnology is increasingly recognized as the next wave in the knowledge-based economy.

Vi er nå inne i en femte teknologisk revolusjon basert på nanoteknologisk produksjon.

“Anyone, I would imagine, who has tried to create a biotech company knows just how important patents are. You learn this when you’re studying, and again at your first job, and if you haven’t done so before, you realize it the first time you meet potential investors .” (Mads Øvlisen, Chariman of the Board of Directors, Novo Nordsik).

Investors in biotechnology firms are well aware of the centrality of patents in the industry and will generally conduct a thorough due diligence prior to taking the decision to invest in a company. Their main concerns are generally two-fold.

Firstly, determining the company’s own IP position. In other words, does it fully own its IP? If not, has it obtained it through a licensing agreement and what are the terms and conditions of such an agreement? Is there likelihood of a dispute over ownership? Have the patents been granted? How wide is the geographical coverage? How broad is the protection and how efficient will they be to keep competitors from copying the product?

Secondly, investors will seek to determine whether the company will have freedom to operate, i.e. whether it will be able to commercialize the product without infringing on the IP rights of others. This will be important for investors to minimize risk of investing in a biotech company.

https://www.wipo.int/sme/en/documents/patents_biotech_fulltext.html

Patentporteføljen til Bergenbio virker sterk og de har flere søknader som enda ikke er godkjent – dette lover godt. I tillegg så har jeg registrert at de holder det de lover mhp guiding

Logdec · april 3, 2020, 7:37pm

Part 7 BergenBio pipeline

BergenBio oppgir følgende faser i deres programoversikt

Discovery
Lead optimisation
Preclincal
Phase 1
Phase 2
Phase 3

Ref Part 2 FDA akselerert program som jeg har postet over.

Når kan BergenBio søke Breakthrough designation?
Breakthrough designation applications are submitted as an amendment to the IND applications, usually prior to end of Phase II meeting

Når kan BergenBio søke Accelerated Approval?
The faster approval relies on use of surrogate endpoints.[1] Drug approval typically requires clinical trials with endpoints that demonstrate a clinical benefit, such as increased survival for cancer patients. Drugs with accelerated approval can initially be tested in clinical trials that use a surrogate endpoint, or something that is thought to predict clinical benefit. Surrogate endpoints typically require less time, and in the case of a cancer patient, it is much faster to measure a reduction in tumor size, for example, than overall patient survival.

Drugs approved under the FDA Accelerated Approval Program still need to be tested in clinical trials using endpoints that demonstrate clinical benefit, and those trials are known as phase 4 confirmatory trials. If the drug later proves unable to demonstrate clinical benefit to patients, the FDA may withdraw approval.[2][3]

Når kan BergenBio søke Priority Review?
Priority review vouchers are currently earned by pharmaceutical companies for the development and approval of drugs treating neglected tropical diseases, rare pediatric diseases, and “medical countermeasures” for terrorism. The voucher can be used for future drugs that could have wider indications for use, but the company is required to pay a fee (approximately $2.8 million) to use the voucher.

When seeking approval for a drug, manufacturers can apply to the FDA for priority review. This is granted when a drug is intended to treat a serious condition and would “provide a significant improvement in safety or effectiveness” over currently available treatments.[1] A priority review voucher can be used when a drug does not fit these requirements, but the company wishes to expedite the review process.[2]

Om vi ser på piplinen under til BergenBio så inneholder denne flere som ligger i slutten av fase 2. Jeg forventer at de søker om «Breakthrough Therapy» for noen av disse.

Pipeline 1 @ Phase 2
bemcentinib
Indication: NSCLC (Non-small cell lung cancer )
Combination: KEYTRUDA
Partner: Merck Inc
Bemcentinib met primary endpoint in first cohort of Phase II NSCLC study in combination with KEYTRUDA®

Pipeline 2 @ Phase 2
bemcentinib
Indication: NSCLC (Non-small cell lung cancer )
Combination: TARCEVA

Pipeline 3 @ Phase 2
bemcentinib
Indication: TNBC (Triple negative breast cancer)
Target: KEYTRUDA
Partner: Merck Inc.

Pipeline 4 @ Phase 2
bemcentinib
Indication: Melanoma
Combination: KEYTRUDA / TAFINLAR, MEKINIST
Partner: Bergen University Hospital

Pipeline 5 @ Phase 2 - Fast Track Designation
bemcentinib
Indication: AML (Acute Myeloid Leukaemia)
Combination: single agent / cytarabine, decitabine

Pipeline 6 @ Soon Phase 2
bemcentinib
Indication: NSCLC (Non-small cell lung cancer)
Combination: docetaxel
Partner: UTSW Medical Center

Pipeline 7 @ Preclinical
BGB149
Indication: Cancer
Target: AXL

Pipeline 8 @ Preclinical - Outlicensed
BGB601
Indication: Cancer
Target: AXL-ADC

Pipeline 9 @ Discovery
Indication: Cancer
Target: undisclosed

Veldig spennende pipeline og mange triggere framover.

Logdec · april 4, 2020, 1:03pm

Part 8 Pipeline 1 @ Phase 2 Non-small-cell lung cancer (NSCLC).

BergenBio’s partner Merck (** Keytruda)

Keytruda, is already one of the best-selling drugs in the world and is well on track to becoming the No. 1 drug by revenue within the next few years. Already been approved to treat a number of different cancer types, Keytruda is poised to play a crucial role in the company’s future sales growth.

Pipeline 1 @ Phase 2 Non-small-cell lung cancer (NSCLC).

For people with localized NSCLC, which means the cancer has not spread outside of the lung, the overall 5-year survival rate is 61%. For regional NSCLC, which means the cancer has spread outside of the lung to nearby areas, the 5-year survival rate is about 35%
If the cancer has spread to distant parts of the body, called metastatic lung cancer, the 5-year survival rate is 6%. But because of new effective treatments, this number is changing.

Professor Hani Gabra MD PhD, Chief Medical Officer of BerGenBio, commented: “I am impressed by these results that clearly demonstrate the durable clinical benefits in this difficult to treat low PD-L1 patient population. Importantly the patients that benefit most match gene signatures that predict poor prognosis and a lack of response to immunotherapy in NSCLC”.

Richard Godfrey, Chief Executive Officer of BerGenBio, commented: “I am delighted to see continued significant patient benefit from bemcentinib in combination with Keytruda. This is the first of three cohorts where we are evaluating this combination in previously treated lung cancer patients and I look forward to reporting data from these additional cohorts in the coming months.”

Current estimates predict that the global NSCLC market size will reach $43.7 billion by 2026

Spennende om BergenBio får Keytruda til å fungere bra…

Mykle · april 4, 2020, 4:18pm

Blir unektelig spennende å få mer data fra cohort b i nsclc. Senest i Juni vet vi mer her. Dersom en andel Keytruda refractory pssienter får effekt vil jeg tro det begynner å klø i fingrene til Merck. Kan ikke forstå annet en at de da vil ha Bemcentinib i sin cocktail.

ListeBot · april 6, 2020, 3:03am

En fersk aksjonærliste for BGBIO er tilgjengelig for Insider-medlemmer. Ikke Insider? Les mer og prøv gratis

larsmkn · april 6, 2020, 12:05pm

Ny artikkel ute hvor forsknings-samarbeid mellom forskere i Sør-Korea, USA og Norge finner at BGB324 (bemcentinib) har effekt på magekreft (pre-klinisk), og foreslår dette som en mulig ny behandling (Obs. må prøves ut først):

ncbi.nlm.nih.gov

Inhibiting the GAS6/AXL axis suppresses tumor progression by blocking the interaction between cancer-associated fibroblasts and cancer cells in gastric carcinoma.

CA Bae, IH Ham, HJ Oh, D Lee, J Woo, SY Son, JH Yoon, JB Lorens, RA Brekken, TM Kim, SU Han, WS Park and H Hur, Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, Apr 2020 02

The effects of cancer-associated fibroblasts (CAF) on the progression of gastric carcinoma (GC) has recently been demonstrated. However, agents targeting the interaction between CAF and GC cells have not been applied in a clinical setting. Here, we examined if inhibition for Axl receptor tyrosine kinase (AXL) can suppress CAF-induced aggressive phenotype in GC.We investigated the function of CAF-derived growth arrest-specific 6 (GAS6), a major ligand of AXL, on the migration and proliferation of GC cells. The effect of the AXL inhibitor, BGB324, on the CAF-induced aggressive phenotype of GC cells was also investigated. In addition, we performed immunohistochemistry to examine the expression of phosphorylated AXL protein in 175 GC tissues and evaluated its correlation with the prognosis.The qPCR and western blot analysis showed that GAS6 expression was higher in CAF relative to other cells. We found that co-culture with CAF increased the phosphorylation of AXL (P-AXL), differentiation into a mesenchymal-like phenotype, and cell survival in GC cell lines. When the expression of AXL was genetically inhibited in GC cells, the effect of CAF was reduced. BGB324, a small molecule inhibitor of AXL, suppressed the effects of CAF on GC cell lines. In GC tissues, high levels of P-AXL were significantly associated with poor overall survival (P = 0.022).We concluded that CAF are a major source of GAS6 and that GAS6 promotes an aggressiveness through AXL activation in GC. We suggested that an AXL inhibitor may be a novel agent for GC treatment.

larsmkn · april 6, 2020, 11:24am

Ny artikkel ute som foreslår at hemming av AXL (som bemcentinib hemmer) eller NFkB kan gjøre MPNST (en sjelden kreft som rammer celler rundt nerver) sensitiv mot andre kinase-hemmere og kjemoterapi:

ncbi.nlm.nih.gov

Kinome Profiling of NF1-Related MPNSTs in Response to Kinase Inhibition and Doxorubicin Reveals Therapeutic Vulnerabilities.

JL Grit, MG Pridgeon, CJ Essenburg, E Wolfrum, ZB Madaj, L Turner, J Wulfkuhle, EF Petricoin, CR Graveel and MR Steensma, Genes, Mar 2020 20

Neurofibromatosis Type 1 (NF1)-related Malignant Peripheral Nerve Sheath Tumors (MPNST) are highly resistant sarcomas that account for significant mortality. The mechanisms of therapy resistance are not well-understood in MPNSTs, particularly with respect to kinase inhibition strategies. In this study, we aimed to quantify the impact of both the genomic context and targeted therapy on MPNST resistance using reverse phase phosphoproteome array (RPPA) analysis. We treated tumorgrafts from three genetically engineered mouse models using MET (capmatinib) and MEK (trametinib) inhibitors and doxorubicin, and assessed phosphosignaling at 4 h, 2 days, and 21 days. Baseline kinase signaling in our mouse models recapitulated an MET-addicted state (NF1-MET), P53 mutation (NF1-P53), and HGF overexpression (NF1). Following perturbation with the drug, we observed broad and redundant kinome adaptations that extended well beyond canonical RAS/ERK or PI3K/AKT/mTOR signaling. MET and MEK inhibition were both associated with an initial inflammatory response mediated by kinases in the JAK/STAT pathway and NFkB. Growth signaling predominated at the 2-day and 21-day time points as a result of broad RTK and intracellular kinase activation. Interestingly, AXL and NFkB were strongly activated at the 2-day and 21-day time points, and tightly correlated, regardless of the treatment type or genomic context. The degree of kinome adaptation observed in innately resistant tumors was significantly less than the surviving fractions of responsive tumors that exhibited a latency period before reinitiating growth. Lastly, doxorubicin resistance was associated with kinome adaptations that strongly favored growth and survival signaling. These observations confirm that MPNSTs are capable of profound signaling plasticity in the face of kinase inhibition or DNA damaging agent administration. It is possible that by targeting AXL or NFkB, therapy resistance can be mitigated.

Morgo26 · april 6, 2020, 11:28am

Thanks for those Lars. Really think Bgbio is onto something with Bemcentinib. I also really think i don’t have anywhere near enough BGBIO shares…

larsmkn · april 10, 2020, 9:51am

Ny artikkel ute i Natur, en av de mest prestisjefylte journalene som finnes, har gjort pre-kliniske forsøk hvor de bekrefter at AXL oppregulerer PD-L1 (immunhemmer) og at behandling med R428 aka. BGB324 aka. bemcentinib blokkere denne oppreguleringen. Dette bekrefter at bemcentinib kan ha en viktig rolle i få immunforsvaret til å angripe kreften. Utrolig kult å finne denne artikkelen i Nature som er blant topp of the topp av journaler:

https://www.nature.com/articles/s41586-020-2134-y

Logdec · april 11, 2020, 12:38pm

Ref over, men noe mere tekst for oss som ikke betaler…

https://www.google.ch/amp/s/www.oncozine.com/new-regulatory-pathway-may-boost-immunotherapy/amp/

New York City’s largest academic medical system, have discovered a pathway that regulates special immune system cells in lung cancer, suppressing them and allowing tumors to grow.

Mykle · april 11, 2020, 3:10pm

Kan dette bety at kan komme et studie med Bemcentinib og Regeneron? Eller misforstår jeg helt?

Checkpoint blockade
The results of the study will be used to designing a clinical trial, to be conducted in collaboration with Regeneron, that is expected to enhance patients’ response to an immunotherapy called checkpoint blockade, by adding a second therapy that blocks the immune regulatory pathway that decreases dendritic cells’ function in tumors.

Regeneron og Sanofi har jo Libtayo…

Ekornet · april 13, 2020, 5:54pm

Ja det kan det! Libtayo Regeneron er PD-L1 hemmeren som man nå skal se om kan potenseres av AXL-hemming.

Libtayo er i samme gruppe medisiner som Keytruda. Ergo vil denne studien være hyperaktuell for Bemcentinib slik jeg ser det, men skulle de velge en annen AXL hemmer så vil konseptet fortsatt kunne vise seg svært verdifullt for Bergenbio. (Med Bemcentinib sin safety profile, at den er selektiv, og i enkel tablettform, den burde være en klar kandidat for studien).

Har også lest mer av selve artikkelen bak nå og er kjempeglad for det som kommer frem der, nemlig at AXL er viktig i måten solide svulster er resistente til ulik type kreftbehandling ved å regulere sitt eget mikromiljø til dets fordel, noe forskerne bak Bergenbio har sagt hele veien. Og at dette nye funnet publiseres i selveste Nature… hva skal man si… helt rått rett og slett

Mykle · april 13, 2020, 6:58pm

Det er vel daiichi sankyo som er nærmest Bergenbio med selektiv axlhemmer. Usikker hvor langt etter de ligger…?
Ettersom Bencentinib har blitt brukt i innledende studier vil det jo være nærliggende å tro at de fortsetter med samme medikament.
Dont fix it if it aint broken…

Libtayo er på oppløpssiden for godkjenning på nsclc. Hva om de også ser på et kombostudie her?

Utelukkende positivt med interesse fra andre produsenter av immunterapi.
Med godkjenning av Libtayo for nsclc, og med Bemcentinib på innerlommen har de plutselig en edge på Mercks Keytruda

Ekornet · april 13, 2020, 8:41pm

Eller hva med en frekk budkrig mellom dem, når tiden er inne, fordi ingen av dem vil la konkurrenten stikke av med Bemcentinib

Daiichi-Sankyo har en svær pipeline med mye forskjellig ser det ut som, hvor det angis 2 stk AXL kombo studier i fase 1, sist oppdatert nå januar. Begge i NSCLC sammen tyrosin kinasehemmere, målrettet behandling, altså ikke samme virkning som PD-L1 hemming/CPI men som regel mot spesifike mutasjoner i tumors DNA. Jeg er nå ikke mye stresset over denne konkurrenten nei

Mykle · april 13, 2020, 9:07pm

Er jo lov å håpe

For meg fremstår det som mer og mer sikkert at Bemcentinib vil finne sin plass. Spørsmålet er mer hvor langt Bergenbio vil kjøre løpet alene, og hva de eventuelt gir ifra seg på veien.

Ekornet · april 13, 2020, 9:31pm

Ja enig, er også svært spent på dette. Tror selskapet er tro til det de skriver om å skape aksjonærverdier, samtidig så vil et eventuelt salg være på betingelse av arbeidsplasser til miljøet medisinene springer ut av, slik jeg tolker filantropen på eiersiden. Om det påvirker negativt tror jeg ikke, de har jo allerede produkajonaavtale på plass India bl.a.

Blir ikke overrasket om de utlisnsererer NSCLC også tar AML mot markedet selv. Eventuelt kunne de kanskje delt opp selskapet da de ulike retningene krever ganske ulike strategier og ikke minst penger. Hva tenker resten her inne om videre strategi for selskapet?

Flottesen · april 13, 2020, 9:37pm

Utlisensierer de bemcentinib så er vel det for alle potensielle indikasjoner. Men da sitter de igjen med resten av porteføljen, antistoffet pluss det utlisensierte til ADC. Pluss diagnostikk. Og endel som de ikke har informert om enda. Det er nok å ta tak i selv om man utlisensierer/selger bemcentinib.

Mykle · april 13, 2020, 9:41pm

Litt usikker hva angår arbeidsplasser. De fleste sitter jo i Oxford.
Mohn begynner jo i tillegg å dra på årene.

Det du skisserer er jeg ikke fremmed for, men spør du meg så kan de selge Bemcentinib, og fokusere på bgb149 og annet de har i pipelinen.

Mykle · april 13, 2020, 9:45pm

Og det begynner å bli en del av de indikasjonene…