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Truqap plus Faslodex approved in Japan for patients with advanced HR-positive breast cancer

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First and only AKT inhibitor approved in Japan for breast cancer patients with specific biomarker alterations (PIK3CA, AKT1 or PTEN). Approval based on CAPItello-291 results which showed Truqap plus Faslodex reduced the risk of disease progression or death by 50% vs. Faslodex alone in the biomarker-altered population.

AstraZeneca’s Truqap (capivasertib) in combination with Faslodex (fulvestrant) has been approved in Japan for the treatment of adult patients with unresectable or recurrent PIK3CA, AKT1, or PTEN-altered hormone receptor (HR)-positive, HER2-negative breast cancer following progression after treatment with endocrine therapy.

The approval by the Japanese Ministry of Health, Labour, and Welfare (MHLW) was based on the results from the CAPItello-291 Phase III trial published in The New England Journal of Medicine.1 In the trial, Truqap in combination with Faslodex reduced the risk of disease progression or death by 50% versus Faslodex alone in patients with tumours harbouring PI3K/AKT pathway biomarker alterations (based on hazard ratio of 0.50, 95% confidence interval 0.38-0.65; p=<0.001; median progression-free survival (PFS) 7.3 versus 3.1 months).1

In Japan, more than 90,000 women were diagnosed with breast cancer in 2022, and more than 17,000 patients died from the disease in the same year.2 Globally, HR-positive breast cancer (expressing estrogen or progesterone receptors, or both), is the most common breast cancer subtype, with more than 65% of tumours considered HR-positive and HER2-low or HER2-negative.3 Collectively, mutations in PIK3CA, AKT1 and alterations in PTEN occur frequently, affecting approximately 50% of patients with advanced HR-positive breast cancer.46 Endocrine therapies are widely used in this setting, often in combination with cyclin-dependent kinase (CDK) 4/6 inhibitors, but some tumours develop resistance to these therapies, underscoring the need for additional combination approaches with endocrine therapy to extend time before the initiation of chemotherapy.7

Masakazu Toi, MD, PHD, Director of Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Japan said: “The approval of capivasertib and fulvestrant signifies a new era of care in advanced hormone receptor-positive breast cancer in Japan, providing a much-needed new treatment option for approximately half of patients in this setting who have tumours harbouring mutations in PIK3CA, AKT1 or alterations in PTEN. It is important for us to detect these specific tumour biomarker alterations in each patient we see, so that they are potentially able to benefit from this important combination to extend the effectiveness of endocrine-based treatment and delay disease progression.”

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: “Breast cancer is the most common cancer among women in Japan, and innovative, new treatment options are urgently needed. Today’s approval of Truqap, a first-in-class AKT-inhibitor, represents a significant step forward for HR-positive breast cancer treatment and an important new option for approximately fifty per cent of patients who have tumours with these specific mutations or alterations.”

In the CAPItello-291 trial, the safety profile of Truqap plus Faslodex was similar to that observed in previous trials evaluating this combination.1

The MHLW have also approved a companion diagnostic test to detect the relevant alterations (PIK3CA, AKT1 and PTEN).

Regulatory applications are currently under review in China, the European Union, and several other countries, and this indication for Truqap in combination with Faslodex is already approved in the US and several other countries based on results from the CAPItello-291 trial.

Financial considerations
Following this approval in Japan, Astex Therapeutics is eligible to receive a milestone payment from AstraZeneca on first commercial sale of the drug in Japan as well as royalties on future sales in line with the agreement between the two companies.

Notes

HR-positive breast cancer
Breast cancer is the second most common cancer and one of the leading causes of cancer-related death worldwide.8 More than two million patients were diagnosed with breast cancer in 2022, with more than 665,000 deaths globally.8

HR-positive breast cancer (expressing estrogen or progesterone receptors, or both), is the most common subtype of breast cancer with more than 65% of tumours considered HR-positive and HER2-low or HER2-negative.3

The growth of HR-positive breast cancer cells is often driven by estrogen receptors (ER), and endocrine therapies that target ER-driven disease are widely used as 1st-line treatment in the advanced setting, and often paired with CDK4/6 inhibitors.7,9,10 However, resistance to CDK4/6 inhibitors and current endocrine therapies develops in many patients with advanced disease.9 Once this occurs, treatment options are limited – with chemotherapy being the current standard of care and survival rates are low with approximately 30% of patients anticipated to live beyond five years after diagnosis.3,9,11

The optimisation of endocrine therapy and overcoming resistance to enable patients to continue benefiting from these treatments, as well as identifying new therapies for those who are less likely to benefit, are active areas of focus for breast cancer research.

CAPItello-291
CAPItello-291 is a Phase III, double-blind, randomised trial evaluating the efficacy of Truqap in combination with Faslodex versus placebo plus Faslodex for the treatment of locally advanced (inoperable) or metastatic HR-positive, HER2-low or negative (immunohistochemistry (IHC) 0 or 1+, or IHC 2+/in-situ hybridisation (ISH)-negative) breast cancer.

The global trial enrolled 708 adult patients with histologically confirmed HR-positive, HER2-low or negative breast cancer whose disease has recurred or progressed during or after aromatase inhibitor therapy, with or without a CDK4/6 inhibitor, and up to one line of chemotherapy for advanced disease. The trial has dual primary endpoints of PFS in the overall patient population and in a population of patients whose tumours have qualifying alterations in the PI3K/AKT pathway (PIK3CA, AKT1 or PTEN genes). In the trial, approximately 40% of tumours had these alterations and approximately 70% of patients received a prior CDK4/6 inhibitor.

Truqap
Truqap is a first-in-class, potent, adenosine triphosphate (ATP)-competitive inhibitor of all three AKT isoforms (AKT1/2/3). Truqap 400mg is administered twice daily according to an intermittent dosing schedule of four days on and three days off. This was chosen in early phase trials based on tolerability and the degree of target inhibition.

Truqap in combination with Faslodex is approved in the US, Japan and several other countries for the treatment of adult patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer with one or more biomarker alterations (PIK3CA, AKT1 or PTEN) based on the results from the CAPItello-291 trial. Eligible patients will have progressed on at least one endocrine-based regimen in the metastatic setting or experienced recurrence on or within 12 months of completing adjuvant therapy.

Truqap is currently being evaluated in Phase III trials for the treatment of multiple subtypes of breast cancer and in other tumour types in combination with established treatments. The ongoing clinical research programme is focused on tumours reliant on signalling via the PI3K/AKT pathway, and in tumours harbouring biomarker alterations in this pathway.

Truqap was discovered by AstraZeneca subsequent to a collaboration with Astex Therapeutics (and its collaboration with the Institute of Cancer Research and Cancer Research Technology Limited).

Faslodex
Faslodex is an endocrine therapy indicated for the treatment of estrogen receptor-positive, locally advanced or metastatic breast cancer in postmenopausal women not previously treated with endocrine therapy, or with disease relapse on or after adjuvant anti-estrogen therapy, or disease progression on anti-estrogen therapy.

In the US, EU and Japan, Faslodex is also approved in combination with CDK4/6 inhibitors for the treatment of women with HR-positive, HER2-negative advanced or metastatic breast cancer, whose cancer has progressed after endocrine medicine. Faslodex represents a hormonal treatment approach that helps to slow tumour growth by blocking and degrading the estrogen receptor – a key driver of disease progression.

Faslodex is approved as monotherapy or in combination with medicines from various drug classes including CDK4/6, PI3K and AKT inhibitors for the treatment of patients with HR-positive advanced breast cancer and is being evaluated in combination with medicines from other drug classes.

AstraZeneca in breast cancer
Driven by a growing understanding of breast cancer biology, AstraZeneca is starting to challenge, and redefine, the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death.

AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumour environment.

With Enhertu (trastuzumab deruxtecan), a HER2-directed antibody drug conjugate (ADC), AstraZeneca and Daiichi Sankyo are aiming to improve outcomes in previously treated HER2-positive and HER2-low metastatic breast cancer and are exploring its potential in earlier lines of treatment and in new breast cancer settings.

In HR-positive breast cancer, AstraZeneca continues to improve outcomes with foundational medicines Faslodex and Zoladex (goserelin) and aims to reshape the HR-positive space with first-in-class AKT inhibitor, Truqap, and next-generation SERD and potential new medicine camizestrant. AstraZeneca is also collaborating with Daiichi Sankyo to explore the potential of TROP2-directed ADC, datopotamab deruxtecan, in this setting.

PARP inhibitor Lynparza (olaparib) is a targeted treatment option that has been studied in early and metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with MSD (Merck & Co., Inc. in the US and Canada) continue to research Lynparza in these settings and to explore its potential in earlier disease.

To bring much-needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is evaluating the potential of datopotamab deruxtecan alone and in combination with immunotherapy Imfinzi (durvalumab), Truqap in combination with chemotherapy, and Imfinzi in combination with other oncology medicines, including Lynparza and Enhertu.

AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @AstraZeneca.

Contacts
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References

  1. Turner N, et al. Capivasertib in Hormone Receptor–Positive Advanced Breast Cancer. NEJM. 2023; 388:2058–70.
  2. World Health Organization. GLOBOCAN Japan Fact Sheet. Available at: https://gco.iarc.who.int/media/globocan/factsheets/populations/392-japan-fact-sheet.pdf. Accessed March 2024. 
  3. National Cancer Institute. Surveillance, Epidemiology and End Results Program. Available at: https://seer.cancer.gov/statfacts/html/breast-subtypes.html. Accessed March 2024. 
  4. Howell S J, et al. Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor-positive, HER2-negative breast cancer (FAKTION). J Clin Oncol. 2022; 23:851-64.
  5. Hortobagyi G N, et al. Correlative Analysis of Genetic Alterations and Everolimus Benefit in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Results From BOLERO-2. J Clin Oncol. 2016; 34:419-26.
  6. Millis S Z, et al. Landscape of phosphatidylinositol-3-kinase pathway alterations across 19784 diverse solid tumors. JAMA Oncol. 2016;2(12):1565-73.
  7. Lin M, et al. Comparative Overall Survival of CDK4/6 Inhibitors Plus Endocrine Therapy vs. Endocrine Therapy Alone for Hormone receptor-positive, HER2-negative metastatic breast cancer. J Cancer. 2020; 10.7150/jca.48944.
  8. World Health Organization. GLOBOCAN Breast Fact Sheet. Available at: https://gco.iarc.who.int/media/globocan/factsheets/cancers/20-breast-fact-sheet.pdf. Accessed March 2024. 
  9. Lloyd M R, et al. Mechanisms of Resistance to CDK4/6 Blockade in Advanced Hormone Receptor–positive, HER2-negative Breast Cancer and Emerging Therapeutic Opportunities. Clin Cancer Res. 2022; 28(5):821-30.
  10. Scabia V, et al. Estrogen receptor positive breast cancers have patient specific hormone sensitivities and rely on progesterone receptor. Nat Commun. 2022; 10.1038/s41467-022-30898-0.
  11. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology (NCCN Guidelines). Available at: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1419. Accessed March 2024
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Botnia Exploration Holding AB (publ) har säkrat lånelöfte om 12 MSEK

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Botnia Exploration Holding AB (publ) har idag undertecknat ett lånelöfte om 12 MSEK från de tre största aktieägarna: Need Invest AB, Ramab AB, och Akilakonsulting AB. Lånelöftet har en giltighetstid om 12 månader från utförandedatum med en ränta om Stibor+2,5% per år.  

Samtidigt har bolaget kommit överens med Norrlandsfonden om att förhandla fram nya villkor gällande förfallodatum på det konvertibla lån om 5,2 MSEK som förfaller till återbetalning 2024-12-31.

Idag är villkoren att konvertering kan ske till och med 2024-10-31 och om inte konvertering skett förfaller lånebeloppet 2024-12-31. De nya överenskomna villkoren är att konvertering kan ske till och med 2027-12-31 och om inte konvertering skett förfaller lånebeloppet 2028-01-31. Inga övriga förändringar i villkoren kommer att ske. 

– Vi är inne i en väldigt intensiv uppstartsfas av vår guldgruva i Fäbodtjärn och då i detta läge kunna förstärka vårt kassaflöde med sammanlagt 17,2 MSEK känns väldigt tillfredsställande. Det finns normalt flertalet tekniska osäkerhetsfaktorer i samband med en gruvstart, men med detta lånelöfte bedömer vi möjligheterna som goda att vi säkerställt kapital fram tills att vi genererar eget positivt kassaflöde. Vi känner en styrka och trygghetskänsla i det förtroende våra största ägare har visat oss, säger Botnia Explorations VD Fredrik Bergsten.  

För ytterligare information kontakta:
Fredrik Bergsten, VD  – Botnia Exploration Holding AB (publ)
Telefon: +46 70 519 34 41
E-post: fredrik.bergsten@botniaexploration.com

Denna information är insiderinformation som Botnia Exploration Holding AB (publ) är skyldigt att offentliggöra enligt EU:s marknadsmissbruksförordning. Informationen lämnades genom ovanstående kontaktpersons försorg, för offentliggörande den 12 april 2024 kl. 20:15 CET

Botnia Exploration Holding AB (publ) är ett prospekteringsbolag med målsättningen att driva småskalig gruvbrytning med fokus på guld och basmetaller i Sverige. Bolaget är listat på Nasdaq First North Growth Market (BOTX). Bolagets Certified Adviser är Carnegie Investment Bank AB (publ). För ytterligare information besök bolagets hemsida www.botniaexploration.com.

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Botnia Exploration Holding AB (publ) publicerar Årsredovisning 2023

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Botnia Exploration Holding AB publicerar idag sin årsredovisning för 2023. 

Årsredovisningen finns tillgänglig på bolagets hemsida Årsredovisningar

För ytterligare information kontakta:
Fredrik Bergsten, VD  – Botnia Exploration Holding AB (publ)
Telefon: +46 70 519 34 41
E-post: fredrik.bergsten@botniaexploration.com

Botnia Exploration Holding AB (publ) är ett prospekteringsbolag med målsättningen att driva småskalig gruvbrytning med fokus på guld och basmetaller i Sverige. Bolaget är listat på Nasdaq First North Growth Market (BOTX). Bolagets Certified Adviser är Carnegie Investment Bank AB (publ). För ytterligare information besök bolagets hemsida www.botniaexploration.com.

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Corem Property Group AB (publ) emitterar seniora icke säkerställda gröna obligationer

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EJ FÖR DISTRIBUTION I ELLER TILL, ELLER TILL NÅGON PERSON SOM BEFINNER SIG I ELLER ÄR BOSATT I USA, DESS TERRITORIUM OCH BESITTNINGAR (INKLUSIVE MEN INTE BEGRÄNSAT TILL PUERTO RICO, DE AMERIKANSKA JUNGFRUÖARNA, GUAM, AMERIKANSKA SAMOA, WAKEÖARNA, NORDMARIANERNA, VARJE DELSTAT I USA OCH DISTRICT OF COLUMBIA) ELLER TILL NÅGON AMERIKANSK PERSON (U.S. PERSON, SÅSOM DEFINIERATS I REGULATION S I UNITED STATES SECURITIES ACT OF 1933, I DESS NUVARANDE LYDELSE) ELLER NÅGON JURISDIKTION DÄR UTGIVANDE, PUBLICERING ELLER DISTRIBUTION AV DETTA DOKUMENT ÄR FÖRBJUDET ENLIGT LAG. DISTRIBUTION AV DETTA DOKUMENT KAN STRIDA MOT LAG I VISSA JURISDIKTIONER (I SYNNERHET USA OCH STORBRITANNIEN)

Corem Property Group AB (publ) (”Corem” eller ”Bolaget”) har framgångsrikt emitterat nya seniora icke säkerställda gröna obligationer om 500 miljoner kronor (de ”Nya Gröna Obligationerna”). De Nya Gröna Obligationerna emitterades under ett ramverk om 2 miljarder kronor, har en löptid om 2,75 år och löper med en rörlig ränta om 3 månaders STIBOR plus 375 baspunkter och slutligt förfall 19 januari 2027. Bolaget avser att ansöka om upptagande till handel av de Nya Gröna Obligationerna på Nasdaq Stockholms företagsobligationslista för hållbara obligationer.

Transaktionslikviden kommer att användas i enlighet med det Gröna Ramverket, inklusive finansiering eller refinansiering av gröna byggnader och investeringar i energieffektivitet, samt inlösen och/eller återköp av Corem Kelly AB (publ)s utestående obligationer och Bolagets utestående obligationer.

Då emissionen sker under Bolagets tysta period har inga investerare mottagit eller haft tillgång till någon ännu ej offentliggjord information avseende Bolaget eller dess verksamhet.

Nordea och Swedbank har agerat joint bookrunners i transaktionen. Walthon har agerat legal rådgivare åt Bolaget.

Corem Property Group AB (publ)
 

FÖR YTTERLIGARE INFORMATION, VÄNLIGEN KONTAKTA
Rutger Arnhult, vd, 070-458 24 70, rutger.arnhult@corem.se
Eva Landén, vice vd, 010-482 76 50, eva.landen@corem.se

Corem Property Group AB (publ)
Box 56085, SE-102 17 Stockholm
Besök: Riddargatan 13 C
Org. nr: 556463-9440
www.corem.se

Detta pressmeddelande har offentliggjorts på svenska och engelska. Vid en eventuell avvikelse mellan språkversionerna ska den svenskspråkiga versionen ha företräde.

Corem Property Group är ett fastighetsbolag som på ett hållbart sätt äger, förvaltar och utvecklar kommersiella fastigheter i storstads- och tillväxtområden. Corem Property Group är noterat på Nasdaq Stockholm, Large Cap.

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