1stOncology™: Cancer Intelligence Service – Page 10775 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

Successful Relocation of Vivoryon Shares Package

On December 14, 2020 Vivoryon Therapeutics N.V. (Euronext Amsterdam: VVY; ISIN DE0007921835) reported that it has been informed by Hauck & Aufhäuser Privatbankiers AG that the remaining stake held by MorphoSys AG, comprising of around 6.5% of the share capital, has been successfully placed on the capital market (Press release, Vivoryon Therapeutics, DEC 14, 2020, View Source [SID1234572793]). Around 1.3 million shares were sold to institutional and qualified investors through private placements. Hauck & Aufhäuser acted as sole bookrunner and placed the shares with a select group of long-term institutional investors across Europe and North America.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

Schedule Your 30 min Free Demo!

Trastuzumab deruxtecan recommended for approval in the EU by CHMP for HER2-positive metastatic breast cancer

On December 14, 2020 AstraZeneca and Daiichi Sankyo Company, Limited (Daiichi Sankyo)’s trastuzumab deruxtecan has been recommended for conditional marketing authorisation in the European Union (EU) as a monotherapy for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 based regimens (Press release, AstraZeneca, DEC 14, 2020, View Source [SID1234572792]).

In Europe, approximately 520,000 cases of breast cancer in women are diagnosed annually, with roughly one in five cases being HER2 positive.1-2 The impact of the disease is significant, with breast cancer responsible for more than 137,000 deaths per year.1

Following review of the application under its accelerated assessment procedure, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) based its positive opinion on results from the registrational DESTINY-Breast01 Phase II trial, which were published in The New England Journal of Medicine, and the results from the Phase I trial published in The Lancet Oncology.3,4 In the DESTINY-Breast01 trial, trastuzumab deruxtecan demonstrated clinically meaningful and durable activity in patients who had received two or more prior anti-HER2 medicines.

An updated analysis from DESTINY-Breast01 was presented last week at the 2020 San Antonio Breast Cancer Symposium, reinforcing the durable efficacy and long-term safety and tolerability profiles of trastuzumab deruxtecan.

José Baselga, Executive Vice President, Oncology R&D, said: "The durable responses demonstrated in the DESTINY-Breast01 trial have never been seen before in this patient setting. If approved by the European Commission, physicians in Europe will have an important new treatment option for patients with previously treated HER2-positive metastatic breast cancer."

Gilles Gallant, Senior Vice President, Global Head, Oncology Development, Oncology R&D, Daiichi Sankyo, said: "We are encouraged by the CHMP positive opinion given the significant unmet need for patients with HER2-positive metastatic breast cancer. Trastuzumab deruxtecan is already available for patients with HER2-positive metastatic breast cancer in the US and Japan, and we are now one step closer to bringing this important new medicine to patients in Europe."

HER2-positive breast cancer

Approximately 520,000 cases of breast cancer are diagnosed in Europe annually, with an estimated one in five cases considered HER2 positive.1-2

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours, including breast, gastric, lung and colorectal cancers. HER2 overexpression may be associated with a specific HER2 gene alteration known as HER2 amplification and is often associated with aggressive disease and a poor prognosis in breast cancer.5

There remain significant unmet clinical needs for patients with HER2-positive metastatic breast cancer. The disease remains incurable with patients eventually progressing after currently available treatment options.6,7

DESTINY-Breast01

DESTINY-Breast01 is a registrational Phase II, single-arm, open-label, global, multicentre, two-part trial testing the safety and efficacy of trastuzumab deruxtecan in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab emtansine. The primary endpoint of the trial is objective response rate, as determined by independent central review. Secondary objectives include duration of response, disease control rate, clinical benefit rate, progression-free survival and overall survival.

Trastuzumab deruxtecan

Trastuzumab deruxtecan is a HER2-directed antibody drug conjugate (ADC). It is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform.

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. Trastuzumab deruxtecan is comprised of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload by a tetrapeptide-based linker.

Trastuzumab deruxtecan is approved under the brand name Enhertu (5.4mg/kg) in the US and Japan for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting based on the DESTINY-Breast01 trial. In September 2020, Enhertu (6.4mg/kg) was approved in Japan for patients with HER2-positive unresectable advanced or recurrent gastric cancer that progressed after chemotherapy based on the DESTINY-Gastric01 trial.

Development programme

A comprehensive development programme is underway globally, with nine registrational trials evaluating the efficacy and safety of trastuzumab deruxtecan monotherapy across multiple HER2 cancers, including breast, gastric and lung cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.

In October 2020, trastuzumab deruxtecan was granted Priority Review from the US Food and Drug Administration for the treatment of patients with HER2-positive metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. In May 2020, trastuzumab deruxtecan received a Breakthrough Therapy Designation (BTD) and Orphan Drug Designation (ODD) for gastric cancer, including GEJ adenocarcinoma.

In May 2020, trastuzumab deruxtecan also received a BTD for the treatment of patients with metastatic non-small cell lung cancer whose tumours have a HER2 mutation and with disease progression on or after platinum-based therapy.

Daiichi Sankyo collaboration

Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialise trastuzumab deruxtecan (a HER2-directed ADC) in March 2019, and datopotamab deruxtecan (DS-1062; a TROP2-directed ADC) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is responsible for manufacturing and supply of trastuzumab deruxtecan and datopotamab deruxtecan.

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. AstraZeneca aims to continue to transform outcomes for HR-positive breast cancer with foundational medicines Faslodex (fulvestrant) and Zoladex (goserelin) and the next-generation SERD and potential new medicine AZD9833. PARP inhibitor, Lynparza (olaparib) is a targeted treatment option for 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 metastatic breast cancer patients with an inherited BRCA mutation and are exploring new opportunities to treat these patients earlier in their disease state. Building on the first approval of Enhertu, a HER2-directed antibody-drug conjugate, in previously treated HER2-positive metastatic breast cancer, AstraZeneca and Daiichi Sankyo are exploring its potential in earlier lines of treatment and in new breast cancer settings. To bring much needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is testing immunotherapy durvalumab in combination with other oncology medicines, including Lynparza and Enhertu, investigating the potential of AKT kinase inhibitor, capivasertib, in combination with chemotherapy, and collaborating with Daiichi Sankyo to explore the potential of TROP2-directed ADC, datopotamab deruxtecan (DS-1062).

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 six scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response, Antibody Drug Conjugates, Epigenetics, and Cell Therapies – 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.

STipe Therapeutics launches with EUR 20 million Series A financing

On September 30, 2019, STipe Therapeutics (STipe), a company founded to exploit a novel approach to the stimulator of interferon genes (STING) Pathway, a major driver of innate immunity, and regulator of tumorigenesis and autoimmune disorders, launched today with an EUR 20 million Series A financing (Press release, STipe Therapeutics, DEC 14, 2020, View Source [SID1234572788]). The round was co-led by Novo Holdings and Arix Bioscience plc who were joined by Wellington Partners Life Science V Fund and Sunstone Life Science Ventures A/S.

STipe was spun out from the Department of Biomedicine, Aarhus University, Denmark in 2018 and is working on harnessing the immune response to target a range of tumours, both directly and in combination with other antitumoral agents. The company is developing first in class drugs targeting intracellular protein-protein interactions of the STING Pathway. STipe’s innovative technology has demonstrated that it can significantly increase the sensitivity of the innate immune system to rapidly detect even a small amount of tumour-DNA. This opens up the potential to induce a synergistic immune response alone or in combination with targeted anticancer therapies, immunotherapy or radiation. STipe has identified potential lead compounds that modulate the STING pathway in a novel way, thereby changing the tumour microenvironment and demonstrating antitumor activity preclinically.

Dr Christian Schetter, Executive Chairman of Stipe and former CEO of Rigontec:
"By assembling a group of world-renowned scientific co-founders, alongside experienced company leadership, STipe has the opportunity to revolutionise the treatment of many cancers. I am delighted to be joining the Company as Executive Chairman and look forward to working with my new colleagues to develop novel cancer therapies using our unique technology."

Dr Claus Elsborg Olesen, Chief Executive Officer of STipe commented:
"The successful financing underscores the potential of our innovative technology and product pipeline. We are grateful for the support from our new shareholders and we look forward to leveraging their extensive experience as we develop multi-product opportunities to target cancer."

Dr Jonathan Tobin, Investment Director at Arix Bioscience commented:
"We are excited about the potential of this novel angle on STING biology that has the potential to greatly enhance the efficacy and safety compared to other innate immune targeting technologies. The combination of the founders’ thorough understanding of the science with Christian Schetter’s experience and leadership in the immunotherapy space makes this a company with a great deal of potential."

Morten Graugaard Døssing, Partner at Novo Holdings added:
"The successful fundraise for STipe Therapeutics is testament to the investors’ appetite for excellent science and technology which ultimately can make a tangible difference to patients’ lives. We have been excited to work closely with STipe Therapeutics for the last three years as part of our company creation efforts and congratulate them on this important milestone.

STipe was cofounded and is led by Chief Executive Officer, Dr Claus Elsborg Olesen, a serial life-science entrepreneur in Denmark with extensive experience in founding and developing biotech companies, alongside the Chief Scientific Officer, Dr Martin Roelsgaard Jakobsen, the founding scientist, and Associate Professor at Aarhus University. In connection with the financing Dr Christian Schetter, former CEO of Rigontec, has joined the Company as Executive Chairman and will be also be joined by new Board members, Morten Graugaard Døssing of Novo Holdings, Jonathan Tobin of Arix Bioscience, Regina Hodits of Wellington Partners, and Sten Verland of Sunstone

SELLAS Announces Pricing of $16.2 Million Registered Direct Offering

On December 13, 2020 SELLAS Life Sciences Group, Inc. (Nasdaq: SLS) ("SELLAS" or the "Company"), a late-stage clinical biopharmaceutical company focused on the development of novel cancer immunotherapies for a broad range of cancer indications, reported that it has entered into a share purchase agreement with institutional investors to purchase approximately $16.2 million of its common stock in a registered direct offering at a purchase price of $7.00 per share (Press release, Sellas Life Sciences, DEC 13, 2020, View Source [SID1234572776]).

Under the terms of the share purchase agreement, SELLAS has agreed to sell 2,320,000 shares of its common stock. The gross proceeds to the Company from the registered direct offering are expected to be approximately $16.2 million before deducting the placement agent’s fees and other offering expenses. The registered direct offering is expected to close on or about December 16, 2020, subject to the satisfaction of customary closing conditions.

Maxim Group LLC is acting as the exclusive lead placement agent in connection with the offering.

The shares of common stock are being offered pursuant to a shelf registration statement on Form S-3 (File No. 333-233869) previously filed and declared effective by the Securities and Exchange Commission (SEC).

This press release does not constitute an offer to sell or the solicitation of an offer to buy, nor will there be any sales of these shares of common stock in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of such jurisdiction. A prospectus supplement relating to the shares of common stock will be filed by SELLAS with the SEC. When available, copies of the prospectus supplement relating to the registered direct offering, together with the accompanying prospectus, can be obtained at the SEC’s website at www.sec.gov or from Maxim Group LLC, 405 Lexington Avenue, New York, NY 10174, Attention: Syndicate Department, or via email at [email protected] or telephone at (212) 895-3745.

TCR2 Announces RECIST Response in Ovarian Cancer from Ongoing Phase 1/2 Trial of TC-210 in Treatment Refractory Mesothelin-Expressing Solid Tumors

On December 13, 2020 TCR2 Therapeutics Inc. (Nasdaq: TCRR), a clinical-stage immunotherapy company with a pipeline of novel T cell therapies for patients suffering from cancer, reported positive interim data from the ongoing Phase 1 portion of the TC-210 ( gavocabtagene autoleucel or "gavo-cel") Phase 1/2 clinical trial for mesothelin-expressing solid tumors (Press release, TCR2 Therapeutics, DEC 13, 2020, View Source [SID1234572799]). As of the November 24, 2020 data cutoff, three PRs according to RECIST 1.1 criteria have been recorded among the first eight patients treated on study, with our first ovarian cancer patient having achieved a confirmed PR up to month six. In addition, the first patient treated at a higher gavo-cel dose (1×108/m2) without lymphodepletion achieved stable disease through two months without any significant toxicities, which has allowed patients to start treatment at that dose with the addition of lymphodepletion. The toxicity profile remains manageable with only two patients to date exhibiting gavo-cel-related non-hematologic grade >2 toxicity and no evidence of neurotoxicity or on-target, off-tumor toxicity. Translational data further demonstrated TRuC-T cell expansion and cytokine induction in all patients.

"Although the focus of any Phase 1 trial is safety, the consistency in tumor regression and RECIST responses we have observed with gavo-cel as a single agent supports our belief in the advantages of TRuC-T cells over other cell therapies and the potential for a fundamentally new approach in the treatment of solid tumors," said Garry Menzel, Ph.D., President and Chief Executive Officer of TCR2 Therapeutics. "The HLA independence of our technology allows us to treat a broad population of patients with mesothelin surface expression while leveraging the full T cell receptor complex to drive enhanced trafficking, on-target killing and persistence in the hostile solid tumor microenvironment. Most important, we are delivering clinical and survival benefit to those patients with heavily pre-treated mesothelioma or ovarian cancer."

"The ability of gavo-cel to benefit patients who have become treatment refractory after having failed multiple lines of therapy, including immune checkpoint inhibitors and anti-mesothelin therapy, combined with its manageable safety profile is remarkable. The changes announced today to the Phase 1 trial design, reducing the intra-cohort safety observation periods to 14 days from 28 days, enable us to more rapidly identify the recommended Phase 2 dose and initiate the Phase 2 expansion trial where we will evaluate the efficacy of gavo-cel in four solid tumor indications. Importantly, in the Phase 2 we will explore the impact of gavo-cel retreatment and its combination with checkpoint inhibitor therapy which could further improve on the clinical benefit observed to date," said Alfonso Quintás-Cardama, M.D., Chief Medical Officer of TCR2 Therapeutics.

The primary objectives of the Phase 1 portion of the study are to define the safety profile of gavo-cel in patients whose tumors overexpress mesothelin and to determine the recommended Phase 2 dose (RP2D). Secondary objectives include ORR and disease control rate (DCR). Exploratory objectives include the assessment of expansion, tumor infiltration, and persistence of gavo-cel.

Summary of trial conduct, baseline characteristics and gavo-cel dose:

Safety Protocol: The new clinical trial protocol amendment allows the intra-cohort safety observation periods to be reduced to 14 days from 28 days, allowing the testing of a gavo-cel dose over a minimum of 56 days compared to the previous 84 days.
Screening: Forty-five percent of patients met the mesothelin expression cut-off as defined per protocol.
Manufacturing: Products meeting protocol defined specifications for gavo-cel have been manufactured successfully for each patient from whom apheresis material was sent into production.
Patient Characteristics: Eight patients received gavo-cel including seven with mesothelioma and one with ovarian cancer with a median age of 65 years (range, 36-84 years). The median number of prior therapies was 5.5 (range, 3-9), including immune checkpoint inhibitor therapy (n=6) and anti-mesothelin therapies (n=3).
Gavo-cel Dose: The eight patients disclosed to date have received gavo-cel at the following dose level (DL):
DL 0: 5×107 cells/m2 without lymphodepletion – 1 mesothelioma
DL 1: 5×107 cells/m2 following lymphodepletion – 5 mesothelioma and 1 ovarian cancer
DL 2: 1×108 cells/m2 without lymphodepletion – 1 mesothelioma
Key clinical findings from the first eight patients treated with gavo-cel:

Safety: Gavo-cel was generally well tolerated, with no patients experiencing neurotoxicity or on-target, off-tumor toxicities. Two (25%) patients experienced Cytokine Release Syndrome (CRS) grade 3, which was successfully managed with tocilizumab and corticosteroids.
Clinical Activity: All eight patients have had at least one disease response assessment. The DCR was 100%, with all patients experiencing tumor regression. The median decrease in the sum of diameters of target lesions was 43% (range, 5% to 75%). The ORR was 38% (2 confirmed and 1 unconfirmed PRs) according to RECIST v1.1 criteria, including one patient who achieved a complete metabolic response.
Translational Data: Peak gavo-cel expansion (Cmax) occurred between days 7 and 23. Cmax increased when gavo-cel was administered following lymphodepletion. The median peak gavo-cel expansion was 811.9 copies/µg of genomic DNA (range, 520 to 5,901 copies/µg). Cytokine induction post-gavo-cel infusion was observed in all evaluable patients, which is indicative of mesothelin target engagement.
About the Phase 1/2 Clinical Trial in Advanced Mesothelin-Expressing Solid Tumors

The Phase 1/2 clinical trial (NCT03907852) is evaluating the safety and efficacy of gavocabtagene autoleucel ("gavo-cel"; TC-210), TCR2’s T cell receptor fusion construct directed against mesothelin. The trial is enrolling patients with mesothelin expressing NSCLC, ovarian cancer, cholangiocarcinoma, and malignant pleural/peritoneal mesothelioma. The Phase 1 dose escalation portion of the clinical trial utilizes a modified 3+3 design with four increasing gavo-cel doses. At each dose, gavo-cel will be tested in two separate dose levels: first without lymphodepletion and then following lymphodepleting chemotherapy. The Phase 1 portion of the clinical trial is ongoing.

In the Phase 2 portion of the clinical trial, approximately 50 patients are planned to receive gavo-cel at the RP2D in four distinct cohorts according to their cancer diagnosis: NSCLC, ovarian cancer, malignant pleural/peritoneal mesothelioma and cholangiocarcinoma. Each cohort will include ten patients, except the NSCLC cohort which will include 20 patients with eight patients to receive gavo-cel as single agent and 12 patients to receive gavo-cel in combination with a programmed cell death 1 (PD-1) blocking antibody.

About Mesothelin-Expressing Solid Tumors

Mesothelin is a cell-surface glycoprotein highly expressed in a wide range of solid tumors, including malignant pleural/peritoneal mesothelioma, ovarian cancer, cholangiocarcinoma, breast cancer, pancreatic cancer and others. Overexpression of mesothelin is associated with poorer prognosis in some cancers due to its active role in both malignant transformation and tumor aggressiveness by promoting cancer cell proliferation, invasion, and metastasis. Of the wide range of solid tumors expressing mesothelin, non-small cell lung cancer, ovarian cancer, mesothelioma and cholangiocarcinoma represent a patient population up to 80,000 annually in the United States alone.

TCR2 Therapeutics Conference Call and Webcast

TCR2 Therapeutics will host a conference call and webcast on Monday, December 14th at 8:00am E.T. The webcast and presentation will be made available on the TCR2 Therapeutics website in the Investors section under Events at View Source Following the live audio webcast, a replay will be available on the Company’s website for approximately 30 days.