On April 2, 2019 Odonate Therapeutics, Inc. (NASDAQ: ODT), a pharmaceutical company dedicated to the development of best-in-class therapeutics that improve and extend the lives of patients with cancer, reported its results of preclinical studies of tesetaxel, Odonate’s investigational, orally administered taxane, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019 (Press release, Odonate Therapeutics, APR 2, 2019, View Source [SID1234534899]). The presentation is entitled, "Tesetaxel, a novel, oral taxane, crosses intact blood-brain barrier (BBB) at therapeutically relevant concentrations" (Poster Board #12; Abstract 3087).

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These preclinical results indicate that, following oral administration, tesetaxel achieves brain concentrations that exceed concentrations required for tumor killing for a sustained period of time. This is in contrast to paclitaxel and docetaxel, the most commonly prescribed taxanes, which do not substantially cross the BBB.

"The development of effective treatment options for patients with brain metastases remains an enormous unmet medical need", said Nancy Lin, M.D., Associate Chief of Breast Oncology, Susan F. Smith Center for Women’s Cancers, and Director of the EMBRACE Metastatic Breast Cancer Program, Dana-Farber Cancer Institute. "Taxanes are one of the most active and widely used classes of chemotherapy agents for the treatment of both early stage and metastatic breast cancer, but conventional taxanes do not cross the blood-brain barrier. The preclinical results showing tesetaxel penetration across an intact blood-brain barrier are compelling and raise the potential for both treatment and prevention of brain metastases. We look forward to investigating the possible translation of this finding into clinical outcomes in CONTESSA, CONTESSA 2 and CONTESSA TRIO, each of which allows enrollment of patients with brain metastases."

About Tesetaxel

Tesetaxel is an investigational, orally administered chemotherapy agent that belongs to a class of drugs known as taxanes, which are widely used in the treatment of cancer. Tesetaxel has several pharmacologic properties that make it unique among taxanes, including: oral administration with a low pill burden; a long (~8-day) terminal plasma half-life in humans, enabling the maintenance of adequate drug levels with relatively infrequent dosing; no history of hypersensitivity (allergic) reactions; and significant activity against chemotherapy-resistant tumors. In patients with metastatic breast cancer, tesetaxel was shown to have significant, single-agent antitumor activity in two multicenter, Phase 2 studies.

About CONTESSA

CONTESSA is a multinational, multicenter, randomized, Phase 3 study of tesetaxel, an investigational, orally administered taxane, in patients with locally advanced or metastatic breast cancer (LA/MBC). CONTESSA is comparing tesetaxel dosed orally at 27 mg/m2 on the first day of each 21-day cycle plus a reduced dose of capecitabine (1,650 mg/m2/day dosed orally for 14 days of each 21-day cycle) to the approved dose of capecitabine alone (2,500 mg/m2/day dosed orally for 14 days of each 21-day cycle) in approximately 600 patients randomized 1:1 with human epidermal growth factor receptor 2 (HER2) negative, hormone receptor (HR) positive LA/MBC previously treated with a taxane in the neoadjuvant or adjuvant setting. Capecitabine is an oral chemotherapy agent that is considered a standard-of-care treatment in LA/MBC. Where indicated, patients must have received endocrine therapy with or without a cyclin-dependent kinase (CDK) 4/6 inhibitor. The primary endpoint is progression-free survival (PFS) as assessed by an Independent Radiologic Review Committee (IRC). CONTESSA’s secondary efficacy endpoints are overall survival (OS), objective response rate (ORR) as assessed by the IRC and disease control rate (DCR) as assessed by the IRC. To learn more, please visit www.contessastudy.com.

About CONTESSA 2

CONTESSA 2 is a multinational, multicenter, Phase 2 study of tesetaxel, an investigational, orally administered taxane, in patients with locally advanced or metastatic breast cancer (LA/MBC). CONTESSA 2 is investigating tesetaxel dosed orally at 27 mg/m2 on the first day of each 21-day cycle plus a reduced dose of capecitabine (1,650 mg/m2/day dosed orally for 14 days of each 21-day cycle) in approximately 125 patients with human epidermal growth factor receptor 2 (HER2) negative, hormone receptor (HR) positive LA/MBC not previously treated with a taxane. Capecitabine is an oral chemotherapy agent that is considered a standard-of-care treatment in LA/MBC. Where indicated, patients must have received endocrine therapy with or without a cyclin-dependent kinase (CDK) 4/6 inhibitor. The primary endpoint is objective response rate (ORR) as assessed by an Independent Radiologic Review Committee (IRC). The secondary efficacy endpoints are duration of response (DoR) as assessed by the IRC, progression-free survival (PFS) as assessed by the IRC, disease control rate (DCR) as assessed by the IRC and overall survival (OS).

About CONTESSA TRIO

CONTESSA TRIO is a multi-cohort, multicenter, Phase 2 study of tesetaxel, an investigational, orally administered taxane, in patients with locally advanced or metastatic breast cancer (LA/MBC). In Cohort 1, approximately 90 patients (with potential expansion to up to 150 patients) with locally advanced or metastatic triple-negative breast cancer (TNBC) who have not received prior chemotherapy for advanced disease will be randomized 1:1:1 to receive tesetaxel dosed orally at 27 mg/m2 on the first day of each 21-day cycle plus either: (1) nivolumab at 360 mg by intravenous infusion on the first day of each 21-day cycle; (2) pembrolizumab at 200 mg by intravenous infusion on the first day of each 21-day cycle; or (3) atezolizumab at 1,200 mg by intravenous infusion on the first day of each 21-day cycle. Nivolumab and pembrolizumab (PD-1 inhibitors) and atezolizumab (a PD-L1 inhibitor) are immuno-oncology (IO) agents approved for the treatment of multiple types of cancer. One of these agents, atezolizumab, in combination with the intravenously delivered taxane, nab-paclitaxel, was recently approved by the U.S. Food and Drug Administration (FDA) as a first-line treatment for patients with metastatic TNBC. The dual primary endpoints for Cohort 1 are objective response rate (ORR) and progression-free survival (PFS). Secondary endpoints include duration of response (DoR) and overall survival (OS). Efficacy results for each of the three PD-(L)1 inhibitor combinations will be assessed for correlation with the results of each of the three approved PD-L1 diagnostic assays. In Cohort 2, approximately 40 elderly patients (with potential expansion to up to 60 patients) with human epidermal growth factor receptor 2 (HER2) negative MBC will receive tesetaxel monotherapy dosed orally at 27 mg/m2 on the first day of each 21-day cycle. The primary endpoint for Cohort 2 is ORR. Secondary endpoints include PFS, DoR and OS. Patients with central nervous system metastases are eligible for both cohorts.

On April 2, 2019 MannKind Corporation (NASDAQ: MNKD), a company focused on the development and commercialization of inhaled therapeutic products for patients with diseases such as diabetes and pulmonary arterial hypertension, reported that it will be featured as a presenting company at the H.C. Wainwright Global Life Sciences Conference at 12:10 PM (CET) on April 8, 2019 (Press release, Mannkind, APR 2, 2019, View Source [SID1234534916]). The conference is being held at the Grosvenor House in London, UK.

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Michael Castagna, Chief Executive Officer, of MannKind Corporation, will provide an overview of the Company’s business during the live presentation and will participate in one-on-one meetings with investors who are registered to attend the conference.

If you are an institutional investor, and would like to attend the Company’s presentation, please click on the following link (www.hcwevents.com ) to register for the conference. Once your registration is confirmed, you will be prompted to log into the conference website to request a one-on-one meeting with the Company.

The presentation will be webcast live. To access the webcast, please visit www.hcwevents.com. Interested parties can also access a link to the live webcast of the presentation from the News & Events section of the Company’s website at View Source The webcast replay will remain available for 14 days following the live presentation.

On April 2, 2019 Synlogic (Nasdaq:SYBX) reported that Aoife Brennan, M.B., B.Ch., Synlogic’s president and chief executive officer, will provide a corporate update at the 18th Annual Needham Healthcare Conference at 3:30 pm ET on Tuesday, April 9, 2019, in New York City (Press release, Synlogic, APR 2, 2019, View Source [SID1234534932]).

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A live webcast of the presentation can be accessed under "Event Calendar" in the Investors & Media section of the Company’s website. An archive copy of the webcast will be available on the Synlogic website for approximately 30 days after the event.

On April 2, 2019 BerGenBio ASA (OSE: BGBIO) reported that the first patient has been dosed in an additional cohort ("Cohort B") of an ongoing phase II open-label study of BerGenBio’s selective AXL inhibitor bemcentinib in combination with Merck’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) in previously treated patients with advanced adenocarcinoma of the lung (NSCLC) (Press release, BerGenBio, APR 2, 2019, View Source [SID1234534951]).

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The additional cohort of the BGBC008 trial, being run in collaboration with Merck (known as MSD outside the US and Canada), will extend eligibility to include patients with previously treated advanced NSCLC whose disease is progressing on immunotherapy.

Patients eligible to participate in Cohort B must have disease progression whilst on a therapy regimen which includes an anti-PD(L)1 inhibitor. The trial follows a two-stage design with the opportunity for an early stop for futility and will evaluate the combination’s objective response rate as a primary endpoint. Comprehensive exploratory studies will evaluate biomarkers in tumour and blood indicative of AXL and PD-L1 expression as well as immune modulation.

Preliminary results from Cohort B are expected in H2 2019. BerGenBio is responsible for conducting the trial. Merck will supply KEYTRUDA for use in the study under a collaboration agreement signed in March 2017.

Richard Godfrey, Chief Executive Officer of BerGenBio, commented: "Throughout 2018, we reported encouraging updates from our ongoing proof-of-concept Phase II clinical trial assessing bemcentinib in combination with KEYTRUDA in advanced lung cancer patients post chemotherapy. Patients with AXL positive disease showed particularly good response rates, supporting our belief that selectively inhibiting AXL may act synergistically with immune checkpoint inhibitors in immunotherapy naïve patients. Pre-clinical and translational data strongly suggest that AXL is implicated in anti-PD(L)-1 (checkpoint-inhibitor) therapy failure which has become a large unmet medical need following the rapid uptake of checkpoint inhibitors in first-line lung cancer therapy. Therefore, I am pleased that we are now extending the ongoing trial to test our hypothesis also in patients showing disease progression on checkpoint inhibitors and I look forward to providing updates on both cohorts during 2019."

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

END

About NSCLC
It is estimated that more than 230,000 new cases of lung cancer have been diagnosed in the US in 2018 and it is the leading cause of cancer deaths. 65% of NSCLCs are of adenocarcinoma pathology. Although various treatments exist for NSCLC, they are often curtailed by acquired resistance to therapy and immune evasion. Novel treatments overcoming these mechanisms in NSCLC are urgently required.

About the BGBC008 trial
The BGBC008 trial is a Phase II open-label study of bemcentinib in combination with KEYTRUDA (pembrolizumab) in previously treated patients with advanced adenocarcinoma of the lung run at centres in the US, UK, Spain and Norway. 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).

Patients eligible for participation in Cohort A must have progressed on or after prior therapy excluding immunotherapy whereas patients in Cohort B will be actively progressing on a therapy regimen containing an anti-PD(L)-1 therapy.

Both cohorts follow a two-stage design, Cohort A has previously successfully progressed into the second stage after meeting its first efficacy endpoint. Cohort B will evaluate advancement into stage 2 after 13 patients have been assessed for response.

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

About AXL
AXL kinase is a cell membrane receptor and an essential mediator of the biological mechanisms that drive aggressive and life-threatening diseases. In cancer, AXL drives tumour survival, treatment resistance and spread, as well as suppressing the body’s immune response to tumours. AXL expression has been established as a negative prognostic factor in many cancers. AXL inhibitors, therefore, have potential value at the centre of cancer combination therapy, addressing significant unmet medical needs and multiple high-value market opportunities.

On April 2, 2019 LIDDS AB reported that Clinical data shows that intratumoral delivery of TLR agonists in combination with immune checkpoint inhibitors can effectively treat solid cancers (Press release, Lidds, APR 2, 2019, View Source [SID1234555907]). NanoZolid technology is very suitable to provide sustained intratumoral release and minimize the need for repeated injections. LIDDS has performed pre-clinical studies with promising results using a TLR9 agonist formulated with NanoZolid.

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Toll-like receptors (TLR) are a key target for the pharmaceutical industry in the fight against cancer. TLRs are expressed on various immune cells, including dendritic cells, and they initiate the body’s immune response. TLR activation can lead to an immunologically active or inflamed tumor environment which then recruits the cytotoxic T-cells necessary for an anti-tumor response in immunotherapy.

-The NanoZolid technology addresses key issues in developing TLR agonists as repeated intratumoral injections are needed using standard formulations, says Monica Wallter, CEO LIDDS.

-We will be focusing our project on TLR9, one of the most promising targets for increasing response and reversing resistance to immunotherapies. TLR9 agonists have been shown to be most effective when injected directly into a tumor, says Monica Wallter.

-A preclinical programme is ongoing to broaden the results obtained to date and we are now preparing for a Phase I clinical trial using NanoZolid combined with a TLR9 agonist. The first human study is planned to commence in 2020, says Monica Wallter.

Preclinical studies have shown that activation of TLR pathways can lead to potent immunological effects that generate anti-tumor immunity and shrink tumors. Most importantly, these effects can act in synergy with immune checkpoint inhibitors.

-There is significant commercial potential in this area of research and drug development and the market for TLR agonists is expected to be worth hundreds of millions of dollars over the coming years, says Monica Wallter.

The most relevant target cancers for the TLR9 project are head and neck cancer, prostate cancer and lymphomas. These cancers are diagnosed in around 2 million patients each year.

Toll-like receptors have been studied for many years and the emerging clinical data suggests that their time has come as important anti-cancer agents when used in combination with immune checkpoint inhibitors.