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Cytokinetics to Present at the Cantor Fitzgerald Global Healthcare Conference

On September 25, 2018 Cytokinetics, Inc. (Nasdaq: CYTK) reported that Robert I. Blum, President and Chief Executive Officer, is scheduled to present a corporate update at the Cantor Fitzgerald Global Healthcare Conference on Tuesday, October 2, 2018 at 10:55 AM ET at the InterContinental New York Barclay Hotel in New York City (Press release, Cytokinetics, SEP 25, 2018, View Source [SID1234529595]).

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Interested parties may access the live webcast of this presentation by visiting the Investors & Media section of the Cytokinetics website at www.cytokinetics.com. The webcast replay of the presentation will be archived on the Presentations page within the Investors & Media section of Cytokinetics’ website for 90 days following the conclusion of the event.

CSPC Pharmaceutical Group Limited and Verastem Oncology Sign Exclusive License Agreement for the Development and Commercialization of COPIKTRA™ (duvelisib) in China

On September 25, 2018 Verastem, Inc. (Nasdaq:VSTM) (Verastem Oncology or the Company), focused on developing and commercializing medicines to improve the survival and quality of life of cancer patients, and CSPC Pharmaceutical Group Limited (HKEx: 1093) (CSPC), a leading pharmaceutical company in China, reported their entry into an exclusive licensing agreement for CSPC to develop and commercialize Verastem Oncology’s COPIKTRA (duvelisib), an oral inhibitor of phosphoinositide 3-kinase (PI3K), and the first approved dual inhibitor of PI3K-delta and PI3K-gamma, for the treatment of all oncology indications in China (Press release, Verastem, SEP 25, 2018, View Source;p=RssLanding&cat=news&id=2368922 [SID1234529591]). COPIKTRA received approval from the U.S. Food and Drug Administration for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) after at least two prior therapies.

COPIKTRA also received accelerated approval for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) after at least two prior systemic therapies. The indication in FL is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Under the terms of the agreement, Verastem Oncology shall receive an upfront payment of $15 Million USD. Verastem Oncology is also entitled to receive additional development milestone payments of $30 Million USD, plus potential sales milestone payments and double-digit percentage royalties based on future net sales of COPIKTRA in China. CSPC will receive exclusive rights to develop and commercialize COPIKTRA and hold the marketing authorization and product license for COPIKTRA in China. CSPC will have the right to collaborate with Verastem Oncology on certain global development and clinical trial activities and will share pro-rata in the cost.

"This agreement with Verastem Oncology brings to our pipeline an overseas approved innovative oncology drug with the potential to help Chinese patients battling cancer, including some high unmet need hematologic malignancies," said Cai Dongchen, Chairman of CSPC. "Our long-standing development and commercial experience in the Chinese pharmaceutical market, together with Verastem Oncology’s expertise with COPIKTRA, will ensure the timely and efficient development of this exciting therapy. At CSPC, we are dedicated to developing and commercializing innovative medicines and we are honored to form this strategic alliance with Verastem Oncology to advance COPIKTRA."

"We are delighted to be working with CSPC, a respected leader in developing, manufacturing and commercializing pharmaceuticals in China," said Robert Forrester, President and Chief Executive Officer of Verastem Oncology. "CSPC successfully markets multiple oncology products, including DUOMEISU (doxorubicin hydrochloride liposome injection), JINYOULI (PEG-rhGCSF injection) and KEAILI (paclitaxel for injection (albumin-bound)). CSPC is a constituent stock of the Hang Seng Index and is recognized as one of the most valuable brands in China. We believe this partnership underscores the global potential of COPIKTRA and complements the growing list of strategic partners focused on bringing COPIKTRA to patients worldwide. As we execute the launch of COPIKTRA in the U.S., we will work collaboratively in parallel with CSPC to rapidly advance COPIKTRA through the hospitals in China and ultimately to cancer patients in need."

About COPIKTRA (duvelisib)

COPIKTRA is an oral inhibitor of phosphoinositide 3-kinase (PI3K), and the first approved dual inhibitor of PI3K-delta and PI3K-gamma, two enzymes known to help support the growth and survival of malignant B-cells. PI3K signaling may lead to the proliferation of malignant B-cells and is thought to play a role in the formation and maintenance of the supportive tumor microenvironment.1,2,3 COPIKTRA is indicated for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) after at least two prior therapies and relapsed or refractory follicular lymphoma (FL) after at least two prior systemic therapies. COPIKTRA is also being developed by Verastem Oncology for the treatment of peripheral T-cell lymphoma (PTCL), for which it has received Fast Track status, and is being investigated in combination with other agents through investigator-sponsored studies.4 For more information on COPIKTRA, please visit www.COPIKTRA.com. Information about duvelisib clinical trials can be found on www.clinicaltrials.gov.

BerGenBio: Updated phII clinical data with selective AXL inhibitor bemcentinib strengthens its potential to improve NSCLC patient outcomes

On September 25, 2018 BerGenBio ASA (OSE:BGBIO) reported its clinical data from its phase II programme with bemcentinib, a first-in-class highly selective oral AXL inhibitor, in non-small cell lung cancer (NSCLC) at the 19th World Conference on Lung Cancer (WCLC) in Toronto, Canada (23-26 September 2018) (Press release, BerGenBio, SEP 25, 2018, View Source [SID1234529585]).

Richard Godfrey, Chief Executive Officer of BerGenBio, commented: "We are extremely encouraged by the data presented at WCLC today. The expanded results from our study combining bemcentinib with the blockbuster immunotherapy KEYTRUDA were particularly promising. In this study, we saw increased response rates in tumours that were positive for AXL versus those that were not. Importantly, we also saw positive responses in tumours that had low or no PD-L1 expression, where we would expect to see little or no effect from KEYTRUDA therapy alone. We are now advancing this study into the second expansion stage.

"Lung cancer remains the largest cancer killer and, despite recent advances with immune-, targeted and combination therapies, many patients are still not benefitting from these treatments. By selectively inhibiting AXL activity with bemcentinib, we aim to block a fundamental survival mechanism that enables cancer cells to evade the immune system and become resistant to therapy. We believe that this approach has the potential to improve patient outcomes to treatment with established and emerging therapies. The encouraging clinical data presented at WCLC investigating bemcentinib with the three major treatment approaches in advanced lung cancer strengthens our belief in bemcentinib and we look forward to providing further updates at leading medical conferences."

The posters presented at WCLC are available on the BerGenBio website in the Investors / Presentations section and a summary of key findings is provided below.

Ph II Study of Oral Selective AXL Inhibitor Bemcentinib (BGB324) in Combination with Pembrolizumab in Patients with Advanced NSCLC
(BerGenBio study reference: BGBC008), James Lorens et al

The BGBC00B study is investigating whether adding bemcentinib to KEYTRUDA (pembrolizumab) in previously treated, PD-L1 unselected and immunotherapy naive patients with advanced adenocarcinoma of the lung is well tolerated and improves patient outcomes. The study will also assess the combination in the subset of PD-L1 negative patients for whom KEYTRUDA is not indicated. A total of 48 patients across two stages will be enrolled.

The first stage is fully enrolled with 24 patients, of which 7 remain on treatment or in follow-up
The biomarker analysis revealed that:
10 of 21 evaluable patients were AXL positive (48%)
Of 20 patients evaluated for PD-L1 expression, 11 (55%) were PD-L1 negative, 7 (35%) were weakly positive and 2 (10%) were strongly positive
40% overall response rate (ORR) was reported in AXL-positive patients with a disease control rate (DCR) of 70%
7 of 10 patients with no PD-L1 expression showed clinical benefit, of which there were 3 PRs (ORR 30%) and 4 SD (DCR70%). This compares with an ORR of 9% in the Keynote-001 study of KEYTRUDA monotherapy in PD-L1 negative patients

Ph I/II Study of Oral Selective AXL Inhibitor Bemcentinib (BGB324) in Combination with Erlotinib in Patients with EGFRm NSCLC
(BerGenBio study reference: BGBC004), Lauren Byers et al

TARCEVA (erlotinib) is indicated for NSCLC that is driven by a mutation in the EGFR gene, the most common mutation in NSCLC. Although response rates to TARCEVA are high initially, nearly all patients develop resistance over time. The BGBC004 study is designed to test if adding bemcentinib to TARCEVA in first- or second-line EGFR mutation-driven NSCLC may prevent or reverse acquired resistance to TARCEVA, respectively.

Patient recruitment into BGBC004 is complete, with 39 patients enrolled across three arms
Arm A – a safety cohort – confirmed a bemcentinib phase II dose (200mg daily) that was well tolerated in combination with full dose TARCEVA over extended periods of time (over two years and ongoing)
Arm B is designed to test whether the addition of bemcentinib to TARCEVA in second line may reverse disease progression in patients whose cancer has become resistant to erlotinib treatment. Arm B met its first primary endpoint, with tumour shrinkage and objective response observed in patients who were negative for the T790M resistance mutation and thus not eligible for any approved targeted therapy (ORR of 20% and a DCR of 40% including 1 PR and 1 SD out of five T790M negative patients)
Arm C is designed to evaluate the ability of bemcentinib to prevent acquired resistance to TARCEVA and improve outcomes in patients who had been responding/stable to first-line TARCEVA therapy. Arm C reported tumour shrinkage in 6 of 9 patients (67%). Importantly, median Progression-Free Survival (PFS), while not mature, had already surpassed median PFS for TARCEVA monotherapy given as a first-line treatment of 10 months.
A Ph I/II Study of Oral Selective AXL Inhibitor Bemcentinib (BGB324) with Docetaxel in Patients with Previously Treated NSCLC
(BerGenBio study reference: BGBIL005), David Gerber et al

Single agent chemotherapy is the last treatment option for NSCLC patients if they fail targeted, immune- and platinum-based chemotherapy regimes. Around 10% of patients show responses to docetaxel single agent chemotherapy with a median PFS of 3-4 months commonly reported. The investigator-sponsored study BGBIL005 is designed to evaluate if combining bemcentinib with docetaxel chemotherapy is safe and can improve outcomes in up to 30 NSCLC patients who have failed up to three lines of therapy.

Among 11 patients evaluated, the combination was generally well tolerated and 2 PRs (18%) and 6 SDs (55%) were reported
A Phase II Study of Oral Selective AXL Inhibitor Bemcentinib (BGB324) in Combination with Pembrolizumab in Patients with Malignant Mesothelioma
(trial not active yet), Dean Fennell et al

The poster described a proposed design for an investigator-sponsored trial (MiST3) evaluating bemcentinib in combination with KEYTRUDA in patients with relapsed malignant mesothelioma. Mesothelioma is a cancer that develops from the thin layer of tissue that covers many of the internal organs and most commonly affects the lining of the lungs and chest wall.

About WCLC
The 19th World Conference on Lung Cancer (WCLC 2018) is the leading meeting on Thoracic Oncology. It is organised by the International Association for the Study of Lung Cancer and will gather more than 7,000 international delegates. WCLC 2018 will take place in Toronto Canada, 23 – 26 September 2018. View Source

About the BGBC008 trial
The BGBC008 trial is a phase II multi-centre open-label study of bemcentinib in combination with KEYTRUDA (pembrolizumab) in previously treated, immunotherapy naive, patients with advanced adenocarcinoma of the lung, the most common form of non-small cell lung cancer (NSCLC). The objective of the trial is to determine the anti-tumour activity of this novel drug combination and responses will be correlated with biomarker status (including AXL kinase and PD-L1 expression).

For more information please access trial NCT03184571 at www.clinicaltrials.gov.

About the BGBC004 trial
The BGBC004 trial is a phase I/II multi-centre open-label study of bemcentinib in combination with TARCEVA (erlotinib) in patients with EGFR mutation driven (EGFRm) Stage IIIb or Stage IV NSCLC. The trial is designed to evaluate reversal of resistance to EGFR targeted therapy in later line patients who are negative for the T790M resistance mutation (arm B) as well as prevention of resistance to TARCEVA in patients receiving the EGFR inhibitor first line (arm C).

For more information please access trial NCT02424617 at www.clinicaltrials.gov.

About the BGBIL005 trial

The BGBIL005 trial is an investigator-led phase I/II study of bemcentinib in combination with docetaxel chemotherapy in previously treated, relapsed / resistant NSCLC patients.

For more information please access trial NCT02922777 at www.clinicaltrials.gov.

About the MiST3 trial
The MiST3 trial is an investigator-led phase II study of bemcentinib in combination with KEYTRUDA in patients with relapsed mesothelioma. The trial, which is not active as of September 2018, is sponsored by the University of Leicester (Leicester, UK), and funded by the British Lung Foundation with support from Merck Sharp and Dohme Limited and BerGenBio. Up to 25 patients are planned to be enrolled at 3
clinical research sites in the UK.

Aduro Biotech to Present at Two Investor Conferences in October

On September 25, 2018 Aduro Biotech, Inc. (NASDAQ: ADRO) reported that Stephen T. Isaacs, chairman, president and chief executive officer of Aduro, will present at the following upcoming investor conferences (Press release, Aduro Biotech, SEP 25, 2018, View Source;p=RssLanding&cat=news&id=2368930 [SID1234529583]):

Cantor Fitzgerald 2018 Global Healthcare Conference in New York, NY on Tuesday, October 2, 2018 at 3:25pm Eastern Time
Leerink Partners Roundtable Series: Rare Disease & Oncology in New York, NY on Wednesday, October 3, 2018 at 8:00am Eastern Time
To access the live webcast and subsequent archived recording of this and other company presentations, please visit Aduro’s website at www.aduro.com.

Daiichi Sankyo Initiates Two Phase 3 Trials of [Fam-] Trastuzumab Deruxtecan (DS-8201) in Patients with HER2 Positive Metastatic Breast Cancer including Head-to-Head Versus T-DM1 and Post-T-DM1 Study

On September 25, 2018 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sanky) reported that the first patients have been dosed in DESTINY-Breast03 and DESTINY-Breast02, two global phase 3 studies evaluating the safety and efficacy of [fam-] trastuzumab deruxtecan (DS-8201), an investigational HER2 targeting antibody drug conjugate (ADC), in patients with previously-treated HER2 positive unresectable and/or metastatic breast cancer (Press release, Daiichi Sankyo, SEP 25, 2018, View Source [SID1234529580]). DESTINY-Breast03 will be a head-to-head comparison of [fam-] trastuzumab deruxtecan versus ado-trastuzumab emtansine (T-DM1), also a HER2 targeting ADC, while DESTINY-Breast02 will assess [fam-] trastuzumab deruxtecan in patients previously treated with standard of care HER2 therapies including T-DM1.

Current treatment guidelines for patients with HER2 positive metastatic breast cancer recommend the combination of trastuzumab, pertuzumab and a taxane as first-line therapy.1,2 For patients whose cancer progresses after initial treatment, T-DM1 is an anti-HER2 agent specifically approved for second-line therapy.1 For cancers that progress after HER2 targeted agents trastuzumab, pertuzumab and T-DM1, there is no specific standard of care. Options for these patients are standard chemotherapy with or without continued anti-HER2 therapy and consideration of palliative care.1

"The DESTINY-Breast03 trial is a key element of our comprehensive development strategy to determine the potential of [fam-] trastuzumab deruxtecan as a second-line therapy in patients with HER2 positive metastatic breast cancer," said Gilles Gallant, BPharm, PhD, Vice President, DS-8201 Global Team Leader, Oncology Research and Development, Daiichi Sankyo. "DESTINY-Breast03 will also help assess whether our investigational and proprietary ADC linker and payload technology used in [fam-] trastuzumab deruxtecan demonstrates clinical relevance when compared to another HER2 targeting ADC currently approved in this setting."

Enrollment into DESTINY-Breast01, the pivotal phase 2 trial evaluating [fam-] trastuzumab deruxtecan in HER2 positive unresectable and/or metastatic breast cancer resistant or refractory to T-DM1 was completed in September 2018, with approximately 230 patients at more than 100 sites in North America, Europe, Japan and other countries in Asia.

About DESTINY-Breast03

DESTINY-Breast03 is a randomized, active-controlled, open-label, multicenter, two-arm, global phase 3 trial designed to compare the safety and efficacy of [fam-] trastuzumab deruxtecan versus T-DM1 in patients with HER2 positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane.

The primary efficacy endpoint of DESTINY-Breast03 is progression-free survival based on blinded independent central review. Secondary efficacy endpoints include overall survival, objective response rate, duration of response, clinical benefit rate and progression-free survival based on investigator assessment. Safety endpoints include serious adverse events, treatment-emergent adverse events and adverse events of special interest. Exploratory efficacy endpoints include duration of stable disease and time to response. Health economics and outcomes research endpoints as well as pharmacokinetic and biomarker endpoints will also be measured.

DESTINY-Breast03 will enroll approximately 500 patients at 150 study sites in North America, Asia and Europe. For more information about the study, visit ClinicalTrials.gov.

About DESTINY-Breast02

DESTINY-Breast02 is a randomized, active-controlled, open-label, multicenter, two-arm, global phase 3 trial designed to compare the safety and efficacy of [fam-] trastuzumab deruxtecan versus investigator’s choice (trastuzumab plus capecitabine or lapatinib plus capecitabine) in patients with HER2 positive unresectable and/or metastatic breast cancer previously treated with standard of care HER2 therapies including T-DM1.

The primary efficacy endpoint of DESTINY-Breast02 is progression-free survival based on blinded independent central review. Secondary efficacy endpoints include overall survival, objective response rate, duration of response, clinical benefit rate and progression-free survival based on investigator assessment. Safety endpoints include serious adverse events, treatment-emergent adverse events and adverse events of special interest. Health economics and outcomes research endpoints as well as pharmacokinetic and biomarker endpoints will also be measured.

DESTINY-Breast02 will enroll up to 600 patients at approximately 160 study sites in North America, South America, Europe and Asia. For more information about the study, visit ClinicalTrials.gov.

About DESTINY-Breast01

DESTINY-Breast01 is a pivotal phase 2, open-label, global, multicenter, two-part study evaluating the safety and efficacy of [fam-] trastuzumab deruxtecan in patients with HER2 positive unresectable and/or metastatic breast cancer previously treated with T-DM1.

The primary endpoint of the study is objective response rate. Secondary objectives include duration of response, disease control rate, clinical benefit rate, progression-free survival and overall survival. The first part of the study includes a pharmacokinetic stage and a dose finding stage to identify the recommended dose of [fam-] trastuzumab deruxtecan to be evaluated in the second part of the study. The second part of the study enrolled patients into one of two cohorts: patients resistant or refractory to T-DM1 (part 2a) and patients who discontinued treatment with T-DM1 for reasons other than resistant or refractory disease (part 2b). For more information about this study, visit ClinicalTrials.gov.

Unmet Need in HER2 Positive Metastatic Breast Cancer

Breast cancer is the second most common cancer worldwide, responsible for approximately 1.67 million of 14.1 million new cases of cancer diagnosed each year.4 Despite improving survival rates over the past 25 years, breast cancer was the fifth leading cause of cancer death overall and was the number one cause of cancer death in women in 2012.3,4For patients diagnosed with metastatic breast cancer, five-year survival rates are low.5

About one in five breast cancers overexpress HER2, a tyrosine kinase receptor growth-promoting protein found on the surface of some cancer cells, which is associated with aggressive disease.4Several unmet needs remain today in HER2 positive metastatic breast cancer. Many tumors advance to the point where no currently approved HER2 targeting treatment continues to control the disease, and there is no current standard of care for HER2 positive tumors after treatment with trastuzumab, pertuzumab and T-DM1.1,6

About [Fam-] Trastuzumab Deruxtecan

[Fam-] trastuzumab deruxtecan (DS-8201; [fam-] trastuzumab deruxtecan in U.S. only; trastuzumab deruxtecan in other regions of world) is the lead product in the investigational ADC Franchise of the Daiichi Sankyo Cancer Enterprise. ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy ("payload") to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. Designed using Daiichi Sankyo’s proprietary ADC technology, [fam-] trastuzumab deruxtecan is comprised of a humanized HER2 antibody attached to a novel topoisomerase I inhibitor payload by a tetrapeptide-based linker. It is designed to target and deliver chemotherapy inside cancer cells and reduce systemic exposure to the cytotoxic payload (or chemotherapy) compared to the way chemotherapy is commonly delivered.

A broad and comprehensive development program with [fam-] trastuzumab deruxtecan is underway in North America, Europe and Asia. In addition to DESTINY-Breast03 and DESTINY-Breast02 phase 3 trials, [fam-] trastuzumab deruxtecan is in pivotal phase 2 clinical development for HER2 positive metastatic breast cancer resistant or refractory to ado-trastuzumab emtansine (DESTINY-Breast01); pivotal phase 2 development for HER2 positive advanced gastric cancer resistant or refractory to trastuzumab (DESTINY-Gastric01); phase 2 development for HER2 expressing advanced colorectal cancer; phase 2 development for metastatic non-squamous HER2 overexpressing or HER2 mutated NSCLC; and, phase 1 development in combination with nivolumab for HER2 expressing metastatic breast and bladder cancer.

[Fam-] trastuzumab deruxtecan has been granted Breakthrough Therapy designation for the treatment of patients with HER2 positive, locally advanced or metastatic breast cancer who have been treated with trastuzumab and pertuzumab and have disease progression after ado-trastuzumab emtansine (T-DM1), and Fast Track designation for the treatment of HER2 positive unresectable and/or metastatic breast cancer in patients who have progressed after prior treatment with HER2 targeted therapies including T-DM1 by the U.S. Food and Drug Administration (FDA). [Fam-] trastuzumab deruxtecan has received SAKIGAKE Designation for the treatment of HER2 positive advanced gastric or gastroesophageal junction cancer by the Japan Ministry of Health, Labour and Welfare (MHLW).

[Fam-] trastuzumab deruxtecan is an investigational agent that has not been approved for any indication in any country. Safety and efficacy have not been established.