On August 21, 2020 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported that congratulates its founder, President and Chief Scientific Officer, Sharon Shacham, PhD, MBA, for being selected as a finalist in the EY Entrepreneur of the Year 2020 New England Awards Program (Press release, Karyopharm, AUG 21, 2020, View Source [SID1234563931]). For more than 30 years, this award has served as one of the world’s most prestigious business awards recognizing entrepreneurs who have disrupted industries, created new product categories and successfully brought innovations that have transformed our world. Dr. Shacham was recognized for her scientific research that led to the development and FDA approval of XPOVIO (selinexor), as well as for leading Karyopharm from its inception to what is now a global pharmaceutical company focused on the discovery, development, and commercialization of novel medicines for patients with cancer and other major diseases.

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"Not only is Dr. Shacham a renowned expert in the biologic mechanisms of cancer and a pioneer in advancing important medical innovations, but she is a true business leader who inspires those around her to achieve extraordinary results," said Michael G. Kauffman, MD, PhD, Chief Executive Officer of Karyopharm. "Under her scientific leadership, we have built a robust research and development organization since our founding in 2008 and have the only nuclear export inhibitor approved in the U.S. This award recognizes the importance of her entrepreneurial spirit and the vital role her leadership and persistence have played in bringing new treatment options to patients battling cancer and other serious diseases."

Dr. Shacham stated, "It’s an honor to be named a finalist for the EY Entrepreneur Of The Year award and I am thrilled to be recognized among the 2020 class of visionary finalists in New England. As we all face unprecedented challenges in our current environment, I think we need entrepreneurs now, more than ever, to help encourage others and solve society’s problems often thought to be insurmountable. I sincerely hope the work we are doing at Karyopharm will not only enable improved clinical outcomes for patients but that we can continue to inspire those around us to set and achieve aspirational goals that will benefit as many people as possible."

The Entrepreneur Of The Year is the world’s most prestigious business awards program for unstoppable entrepreneurs. These visionary leaders deliver innovation, growth and prosperity that transform our world. The program engages entrepreneurs with insights and experiences that foster growth. It connects them with their peers to strengthen entrepreneurship around the world. For more information please visit View Source

About Sharon Shacham, PhD, MBA

Dr. Shacham founded Karyopharm in 2008 and has served as our Chief Scientific Officer and President of Research and Development since December 2012. From 2010 to 2012, Dr. Shacham served as our Chief Scientific Officer and Head of Research and Development, and prior to that, as our President and Chief Executive Officer. Dr. Shacham has led our scientific progress since inception.

Prior to joining Karyopharm, Dr. Shacham served as Senior Vice President of Drug Development at Epix Pharmaceuticals, Inc., and Director, Algorithm and Software Development at Predix Pharmaceuticals Inc., which merged into Epix Pharmaceuticals in 2006, and where she led the company’s efforts in GPCR modeling, computational chemistry, lead optimization and development of clinical trials.

Dr. Shacham holds a Bachelor of Science in Chemistry, along with a Doctor of Philosophy in Biophysical Chemistry and a Master of Business of Administration from Tel Aviv University.

About XPOVIO (selinexor)

XPOVIO is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein exportin 1 (XPO1, also called CRM1). XPOVIO blocks the nuclear export of tumor suppressor, growth regulatory and anti-inflammatory proteins, leading to accumulation of these proteins in the nucleus and enhancing their anti-cancer activity in the cell. The forced nuclear retention of these proteins can counteract a multitude of the oncogenic pathways that, unchecked, allow cancer cells with severe DNA damage to continue to grow and divide in an unrestrained fashion. Karyopharm received accelerated U.S. Food and Drug Administration (FDA) approval of XPOVIO in July 2019 in combination with dexamethasone for the treatment of adult patients with relapsed refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody. Karyopharm has also submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) with a request for conditional approval of selinexor in this same RRMM indication. Karyopharm’s supplemental New Drug Application (sNDA) requesting an expansion of its current indication to include the treatment for patients with multiple myeloma after at least one prior line of therapy has been accepted for filing by the FDA. In June 2020, Karyopharm received accelerated FDA approval of XPOVIO for its second indication in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. Selinexor is also being evaluated in several other mid-and later-phase clinical trials across multiple cancer indications, including as a potential backbone therapy in combination with approved myeloma therapies (STOMP), in liposarcoma (SEAL) and in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with approved therapies in a variety of tumor types to further inform Karyopharm’s clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.

On August 21, 2020 Myriad Genetics, Inc. (NASDAQ: MYGN), a global leader in molecular diagnostics and precision medicine, reported that the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) has exclusively included Myriad’s myChoice CDx test in its new recommendations on the use of PARP inhibitors for the treatment and management of certain patients with advanced ovarian cancer (Press release, Myriad Genetics, AUG 21, 2020, View Source [SID1234563929]). The new recommendations, based on clinical trial results, were published in the Journal of Clinical Oncology.

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The guideline, titled "PARP Inhibitors in the Management of Ovarian Cancer: ASCO (Free ASCO Whitepaper) Guideline," where myChoice CDx was the only named commercial companion diagnostic, states that women with ovarian cancer and germline or somatic mutations in BRCA1 or BRCA2 genes and/or genomic instability – as determined by Myriad myChoice CDx – are recommended by ASCO (Free ASCO Whitepaper) for PARP inhibitor therapy. The guideline includes myChoice CDx guided management in both newly diagnosed and recurrent ovarian cancer.

"We are thrilled to be a part of the rapidly changing landscape in guiding treatment for patients with ovarian cancer. The new ASCO (Free ASCO Whitepaper) guidelines highlight the large number of recent studies that have gone into improving ovarian cancer patient outcomes," said Thomas Slavin, M.D., FACMG, DABCC, senior vice president of Medical Affairs for Myriad Oncology.

According to the American Cancer Society, ovarian cancer ranks fifth in cancer deaths among women, accounting for more deaths than any other cancer of the female reproductive system. In the United States, it is estimated there will be 21,750 new cases diagnosed and around 13,940 deaths in 2020. A woman’s risk of getting ovarian cancer during her lifetime is about one in 78 and the chance of dying from ovarian cancer is about one in 108.

About Myriad myChoice CDx
Myriad’s myChoice CDx is the most comprehensive homologous recombination deficiency test, enabling physicians to identify patients with tumors that have lost the ability to repair double-stranded DNA breaks, resulting in increased susceptibility to DNA-damaging drugs such as platinum drugs or PARP inhibitors. The myChoice CDx test comprises tumor sequencing of the BRCA1 and BRCA2 genes and a composite of three proprietary technologies (loss of heterozygosity, telomeric allelic imbalance and large-scale state transitions). For more information, visit: View Source

On August 21, 2020 Vaccibody AS, a clinical-stage biopharmaceutical company dedicated to the discovery and development of unique immunotherapies, reported 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 (Press release, Vaccibody, AUG 21, 2020, View Source [SID1234563927]).

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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 (Free SITC Whitepaper) 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."

On August 21, 2020 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that it has obtained approval for anti-HER2 antibody-tubulin polymerization inhibitor conjugate Kadcyla Intravenous Infusion 100 mg and 160 mg [generic name: trastuzumab emtansine (genetical recombination)] from the Ministry of Health, Labour and Welfare for an additional indication of HER2-positive postoperative breast cancer (Press release, Chugai, AUG 21, 2020, View Source [SID1234563924]).

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"It is said that the prognosis is poor when pathologic complete response (pCR) is not obtained by neoadjuvant therapy in the treatment of HER-2 positive early breast cancer. In the KATHERINE study, which was evaluated for regulatory approval, Kadcyla reduced the risk of invasive breast cancer recurrence or death from any cause by 50% compared to Herceptin. We are very pleased that this approval addresses an unmet medical need for patients seeking a cure, and contributes to the advancement of treatment," said Dr. Osamu Okuda, Chugai’s President and COO. "As a leading company in the field of oncology, Chugai will strive to promote the appropriate use of this treatment for the benefit of patients."

This approval is based on the results from an open-label, randomized, global phase III KATHERINE study. The study evaluated the efficacy and safety of Kadcyla adjuvant therapy in 1,486 patients with HER2-positive early breast cancer who did not have pathologic complete response following neoadjuvant therapy including Herceptin. The results confirmed the superiority of Kadcyla over Herceptin in terms of the primary endpoint of invasive disease-free survival (unstratified hazard ratio: 0.50 [95% confidence interval: 0.39-0.64, log-rank test, p<0.0001]). The safety profile of Kadcyla in this study was consistent with those observed in the previously approved treatement of HER2-positive metastatic breast cancer, and Kadcyla was also well-tolerated as an adjuvant treatment in HER2-positive early breast cancer.

Reference
Chugai Files for Additional Indication for Anti-HER2 Antibody Drug Conjugate Kadcyla for Adjuvant Therapy of HER2-Positive Early Breast Cancer (Press release issued on August 30, 2019)
View Source

Prescribing Information *The underlined parts were newly added.

Product name: Kadcyla Intravenous Infusion 100 mg
Kadcyla Intravenous Infusion 160 mg
Generic name: trastuzumab emtansine (genetical recombination)
Indications:
HER2-positive inoperable or recurrent breast cancer
HER2-positive postoperative breast cancer
Precautions concerning indications:

1. HER2 testing should be conducted by a pathologist or testing facility with the necessary experience.
2. Administer Kadcyla to patients who have already received trastuzumab (genetical recombination) and chemotherapy with a taxane antineoplastic agent.
3. The efficacy and safety of Kadcyla in pre-operative drug treatment have not been established.

4. This drug should be used for patients for whom a pathological complete response (pCR) has not been obtained by pre-operative drug treatment
5. Select Kadcyla-eligible patients based on a thorough understanding of the efficacy and safety of Kadcyla by carefully reviewing the definition of pCR and other relevant information for patients enrolled in the clinical studies described in "17. CLINICAL STUDIES."
Dosage and administration:
The usual adult dosage is 3.6 mg/kg (body weight) trastuzumab emtansine (genetical recombination) administered by intravenous infusion every 3 weeks. However, in the case of post-operative breast cancer drug treatment, the number of doses is up to 14 times.
About Kadcyla
Kadcyla is an antibody-drug conjugate. It comprises of the anti-HER2 humanized monoclonal antibody, trastuzumab, and a chemotherapeutic drug, DM1, attached together using a stable linker. Kadcyla is designed to target HER2, inhibit HER2 signaling, induce antibody-dependent cell mediated cytotoxicity, and deliver the chemotherapeutic drug DM1 directly inside HER2-positive cancer cells. Once Kadcyla is taken up by those cancer cells, it is designed to destroy them by the DM1. Kadcyla was approved for the adjuvant treatment of patients with HER2-positive early breast cancer with residual invasive disease after neoadjuvant treatment in the U.S. in May 2019 and in EU in December 2019.

On August 21, 2020 AstraZeneca’s Imfinzi (durvalumab) reported that it has been approved in Japan for the treatment of patients with extensive-stage small cell lung cancer (ES-SCLC), in combination with etoposide plus a choice of platinum chemotherapy (either carboplatin or cisplatin) (Press release, AstraZeneca, AUG 21, 2020, View Source [SID1234563923]). SCLC is a highly aggressive, fast-growing form of lung cancer that typically recurs and progresses rapidly, despite initial response to chemotherapy.1,2

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The approval by the Japanese Ministry of Health, Labour and Welfare was based on positive results from the Phase III CASPIAN trial, showing Imfinzi plus chemotherapy demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) versus chemotherapy alone. These results were published in The Lancet in 2019.3

Makoto Nishio MD, PhD, Director, Thoracic Medical Oncology, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan and an investigator in the Phase III CASPIAN trial, said: "Patients with extensive-stage small cell lung cancer in Japan are in urgent need of new options that can provide long-term tumour control and sustained improvements in overall survival. This approval of Imfinzi provides Japanese patients with a new, effective and well-tolerated 1st-line treatment option for this disease, and for the first time physicians have the opportunity to combine immunotherapy with cisplatin for these patients."

Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: "This approval of Imfinzi provides an important new immunotherapy option in Japan for patients with extensive-stage small cell lung cancer. These patients have an especially poor prognosis, with only two per cent surviving beyond five years. Imfinzi, in combination with chemotherapy, delivers a sustained survival benefit and prolonged treatment response with a convenient dosing regimen given every four weeks during maintenance."

The CASPIAN trial met the primary endpoint of OS for Imfinzi plus chemotherapy in June 2019, reducing the risk of death by 27% versus chemotherapy alone (based on a hazard ratio [HR] of 0.73; 95% confidence interval [CI] 0.59-0.91; p=0.0047), with median OS of 13.0 months versus 10.3 months for chemotherapy alone. Results also showed an increased confirmed objective response rate for Imfinzi plus chemotherapy (68% versus 58% for chemotherapy alone) and that Imfinzi added to chemotherapy delayed the time for disease symptoms to worsen.

An updated analysis recently showed sustained efficacy for Imfinzi plus chemotherapy after a median follow up of more than two years (OS HR: 0.75; 95% CI 0.62-0.91; nominal p=0.0032), with median OS of 12.9 months versus 10.5 months for chemotherapy alone. The safety and tolerability for Imfinzi plus chemotherapy were consistent with the known safety profile of these medicines. No patients tested positive for treatment-emergent anti-drug antibodies to Imfinzi.

The efficacy and safety results for Japanese patients in the CASPIAN trial were consistent with the overall trial population in a prespecified analysis. The CASPIAN trial used a fixed dose of Imfinzi (1,500mg), administered every three weeks for four cycles while in combination with chemotherapy and then every four weeks until disease progression.

Imfinzi, in combination with etoposide and either carboplatin or cisplatin, is also approved in the US and several other countries around the world for the treatment of ES-SCLC in the 1st-line setting and is currently under regulatory review in other countries. It was recently recommended for marketing authorisation in the EU for this indication.

As part of a broad development programme, Imfinzi is also being tested following concurrent chemoradiation therapy in patients with limited-stage SCLC in the Phase III ADRIATIC trial.

Small cell lung cancer

Lung cancer is the leading cause of cancer death among both men and women and accounts for about one fifth of all cancer deaths.4 In Japan, nearly 119,000 people were diagnosed with lung cancer in 2018 and there were nearly 82,000 deaths from the disease.5 Lung cancer is broadly split into non-small cell lung cancer (NSCLC) and SCLC, with about 15% classified as SCLC.6 About two thirds of SCLC patients are diagnosed with ES-SCLC, in which the cancer has spread widely through the lung or to other parts of the body.7 Prognosis is particularly poor, as only 6% of all SCLC patients will be alive five years after diagnosis.7

CASPIAN

CASPIAN was a randomised, open-label, multi-centre, global Phase III trial in the 1st-line treatment of 805 patients with ES-SCLC. The trial compared Imfinzi in combination with etoposide and either carboplatin or cisplatin chemotherapy, or Imfinzi and chemotherapy with the addition of a second immunotherapy, tremelimumab, versus chemotherapy alone. In the experimental arms, patients were treated with four cycles of chemotherapy. In comparison, the control arm allowed up to six cycles of chemotherapy and optional prophylactic cranial irradiation. The trial was conducted in more than 200 centres across 23 countries, including the US, in Europe, South America, Asia and the Middle East. The primary endpoint was OS in each of the two experimental arms. In June 2019, AstraZeneca announced the CASPIAN trial had met one primary endpoint of demonstrating OS for Imfinzi plus chemotherapy at a planned interim analysis. In March 2020, it was announced that the second experimental arm with tremelimumab did not meet its primary endpoint of OS.

Imfinzi

Imfinzi is a human monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.

Imfinzi is approved in the curative-intent setting of unresectable, Stage III NSCLC after chemoradiation therapy in the US, Japan, China, across the EU and in many other countries, based on results from the Phase III PACIFIC trial. Imfinzi is also approved for previously treated patients with advanced bladder cancer in the US and a small number of other countries.

As part of a broad development programme, Imfinzi is also being tested as a monotherapy and in combinations including with tremelimumab, an anti-CTLA4 monoclonal antibody and potential new medicine, as a treatment for patients with NSCLC, SCLC, bladder cancer, head and neck cancer, liver cancer, biliary tract cancer, cervical cancer, ovarian cancer, endometrial cancer and other solid tumours.

AstraZeneca in lung cancer

AstraZeneca has a comprehensive portfolio of approved and potential new medicines in late-stage development for the treatment of different forms of lung cancer spanning different histologies, several stages of disease, lines of therapy and modes of action. AstraZeneca aims to address the unmet needs of patients with EGFR-mutated tumours as a genetic driver of disease, which occur in 10-15% of NSCLC patients in the US and EU and 30-40% of NSCLC patients in Asia, with the approved medicines Iressa (gefitinib) and Tagrisso (osimertinib) and its ongoing Phase III trials LAURA, NeoADAURA and FLAURA2.8-10

AstraZeneca is committed to addressing tumour mechanisms of resistance through the ongoing Phase II trials SAVANNAH and ORCHARD, which are testing Tagrisso in combination with savolitinib, a selective inhibitor of c-MET receptor tyrosine kinase, along with other potential new medicines. Enhertu (trastuzumab deruxtecan), a HER2-directed antibody drug conjugate, is in development for the treatment of metastatic non-squamous HER2-overexpressing or HER2-mutated NSCLC, including trials in combination with other anticancer treatments. In addition, DS-1062, a trophoblast cell-surface antigen 2 (TROP2)-directed ADC, is in early development for the treatment of advanced NSCLC where TROP2 is overexpressed in the majority of tumours.11

An extensive Immuno-Oncology (IO) development programme focuses on lung cancer patients without a targetable genetic mutation, which represents up to three-quarters of all patients with lung cancer.12 Imfinzi, an anti-PDL1 antibody, is in development for patients with advanced disease (Phase III trials POSEIDON and PEARL) and for patients in earlier stages of disease, including potentially-curative settings (Phase III trials MERMAID-1, AEGEAN, ADJUVANT BR.31, PACIFIC-2, PACIFIC-4, PACIFIC-5, and ADRIATIC) both as monotherapy and in combination with tremelimumab and/or chemotherapy. Imfinzi is also in development in the Phase II trials NeoCOAST, COAST and HUDSON in combination with potential new medicines from the early-stage pipeline, including Enhertu.

AstraZeneca’s approach to IO

IO is a therapeutic approach designed to stimulate the body’s immune system to attack tumours. The Company’s IO portfolio is anchored by immunotherapies that have been designed to overcome anti-tumour immune suppression. AstraZeneca is invested in using IO approaches that deliver long-term survival for new groups of patients across tumour types.

The Company is pursuing a comprehensive clinical-trial programme that includes Imfinzi as a monotherapy and in combination with tremelimumab in multiple tumour types, stages of disease, and lines of therapy, and where relevant using the PD-L1 biomarker as a decision-making tool to define the best potential treatment path for a patient. In addition, the ability to combine the IO portfolio with radiation, chemotherapy, small targeted molecules from across AstraZeneca’s Oncology pipeline, and from research partners, may provide new treatment options across a broad range of tumours.

AstraZeneca in oncology

AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With seven new medicines launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.