On March 1, 2022 Thermo Fisher and Symphogen reported that extend their collaboration using innovative and efficient workflows to improve data confidence, aiding the creation of new cancer treatments (Press release, Lifescience Newswire, MAR 1, 2022, View Source [SID1234609244])

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Thermo Fisher Scientific, the world leader in serving science, and Symphogen, an affiliate of and the antibody center of excellence within the international pharmaceutical company Servier, announce the continuation of their collaboration to provide biopharmaceutical discovery and development laboratories with innovative tools and streamlined workflows for efficient characterization of complex therapeutic proteins.

Since the collaboration began in 2018, Symphogen has adopted new and innovative instruments and software to improve data quality and processes to develop, test and routinely implement platform workflows for intact and native mass analysis of therapeutic monoclonal antibody (mAb) mixtures. Most recently, the implementation of the Thermo Scientific Orbitrap Exploris MX Mass Detector allows for the highest level of data confidence and an efficient workflow, with seamless method transfer from development instruments. This new system adds to Symphogen’s range of High-Resolution Accurate Mass (HRAM) mass spectrometry technologies, including the Thermo Scientific Q Exactive Plus Orbitrap Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) system and the Thermo Scientific Orbitrap Exploris 240 and 480 Mass Spectrometers. These systems will be controlled using the Thermo Scientific Chromeleon Chromatography Data System (CDS) software, allowing secure, remote operations and data processing from anywhere in the world, providing working flexibility and improved data protection.

"The extension of our collaborative relationship with Symphogen demonstrates our continued commitment to solve tangible scientific challenges within the biopharmaceutical industry," said Eric Grumbach, director biopharma, pharma business, chromatography and mass spectrometry, Thermo Fisher. "Further investment in this collaboration enables critical insights that feed directly into the development of new analytical tools, providing meaningful impact to the characterization of complex biotherapeutics."

Dan Bach Kristensen, principal investigator, Symphogen, said, "Mass spectrometry is playing an increasingly important role in biopharmaceutical development at Symphogen, as exemplified in 2021, when we analyzed over 10,000 biopharmaceutical samples by intact mass analysis on our Orbitrap mass spectrometers. A multitude of separation techniques are now routinely hyphenated to our mass spectrometers, providing unrivalled insight into product quality, from early discovery to late-stage clinical development."

For more information about Thermo Fisher’s chromatography and mass spectrometry workflows for biopharmaceutical characterization, please visit www.thermofisher.com/biopharma. To learn more about the collaboration between Thermo Fisher and Symphogen, please visit www.thermofisher.com/symphogen.

On March 1, 2022 UroGen Pharma Ltd. (Nasdaq: URGN), a biotech company dedicated to developing and commercializing innovative solutions that treat urothelial and specialty cancers, reported the submission of an Investigational New Drug application (IND) for UGN-301 (zalifrelimab) to the U.S. Food and Drug Administration (FDA) in support of the planned initiation of a multi-arm, Phase I clinical study for its anti-CTLA4 antibody (Press release, UroGen Pharma, MAR 1, 2022, View Source [SID1234609243]). The study is expected to begin in the second quarter of 2022 and will evaluate the safety and tolerability of UGN-301 as monotherapy and in combination with other immunomodulators and chemotherapies in recurrent non-muscle invasive bladder cancer (NMIBC). This clinical program builds on encouraging preclinical data showing that intravesical administration of anti-CTLA4 and a TLR agonist leveraging the RTGel platform can produce clinical benefit in the setting of high-grade bladder cancer. It will take approximately 12 months to complete the monotherapy arm of the study.

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"UroGen has shown that combination immunotherapy, when delivered intravesically, is potentially synergistic. While CTLA-4 has long been considered a good target for overcoming the immune suppression produced by tumor cells, anti-CTLA4 antibodies are associated with toxicities when administered systemically," said Mark Schoenberg, Chief Medical Officer, UroGen Pharma. "Local delivery using our RTGel proprietary technology may permit us to leverage the power of a potent antibody while avoiding the toxicity associated with intravenous administration. This is critical because anti-CTLA4 antibodies stimulate cytotoxic T cells while inhibiting suppressive T-regulatory cells, making this class a potentially more comprehensively acting immunomodulator than antibodies to PD-1 and PD-L1."

In the nonclinical study of UGN-301 in cynomolgus monkeys, UroGen assessed the potential toxicity via instillation into the urinary bladder delivered with RTGel reverse thermal hydrogel. The results showed that instillation of UGN-301 at different dose concentrations for a pre-defined period was not associated with mortality, changes in body weights, organ weight differences or meaningful changes among other endpoints, or macroscopic or microscopic findings following a specified recovery period.

According to Dr. Schoenberg, "We view intravesical delivery of our anti-CTLA4 antibody UGN-301 as a cornerstone of the urologic cancers program that we are pursuing in collaboration with MD Anderson Cancer Center, and we are thrilled at the prospect of advancing this program in the form of a multi-arm, Phase 1 study of UGN-301 in combination with other agents. We believe that this approach is unique and leverages our proprietary drug delivery technology and provides an opportunity to evaluate a variety of novel immunomodulatory drug combinations."

On March 1, 2022 Lineage Cell Therapeutics, Inc. (NYSE American and TASE: LCTX), a clinical-stage biotechnology company developing allogeneic cell therapies for unmet medical needs, reported that it will report its fourth quarter and full year 2021 financial and operating results on Thursday, March 10, 2022, following the close of the U.S. financial markets (Press release, Lineage Cell Therapeutics, MAR 1, 2022, View Source [SID1234609242]). Lineage management will also host a conference call and webcast on Thursday, March 10, 2022, at 4:30 p.m. Eastern Time/1:30 p.m. Pacific Time to discuss its fourth quarter and full year 2021 financial and operating results and to provide a business update.

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Interested parties may access the conference call by dialing (866) 888-8633 from the U.S. and Canada and (636) 812-6629 from elsewhere outside the U.S. and Canada and should request the "Lineage Cell Therapeutics Call". A live webcast of the conference call will be available online in the Investors section of Lineage’s website. A replay of the webcast will be available on Lineage’s website for 30 days and a telephone replay will be available through March 18, 2022, by dialing (855) 859-2056 from the U.S. and Canada and (404) 537-3406 from elsewhere outside the U.S. and Canada and entering conference ID number 7718167.

On March 1, 2022 Alexion, AstraZeneca’s Rare Disease group, reported that it has closed an exclusive global collaboration and licence agreement with Neurimmune AG for NI006, an investigational human monoclonal antibody currently in Phase Ib development for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM), an underdiagnosed, systemic condition that leads to progressive heart failure and high rate of fatality within four years from diagnosis (Press release, AstraZeneca, MAR 1, 2022, View Source [SID1234609230]).1,2

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Alexion has been granted an exclusive worldwide licence to develop, manufacture and commercialise NI006.

NI006 is an ATTR depleter that specifically targets tissue-deposited, misfolded transthyretin, with the potential to treat patients with advanced ATTR-CM. NI006 adds a novel and complementary approach to AstraZeneca and Alexion’s pipeline of investigational therapies focused on amyloidosis and strengthens the Company’s broader commitment to addressing cardiomyopathies that can lead to heart failure (HF).

Financial considerations
Under the terms of the agreement, the upfront payment from Alexion to Neurimmune is $30m. Alexion will make additional contingent milestone payments of up to $730m upon achievement of certain development, regulatory and commercial milestones. It will also pay low-to-mid teen royalties on net sales of any approved medicine resulting from the collaboration.

Neurimmune will continue to be responsible for completion of the current Phase Ib clinical trial on behalf of Alexion, and Alexion will pay certain trial costs. Alexion will be responsible for further clinical development, manufacturing and commercialisation following the Phase Ib trial.

Notes

Heart failure
HF is a life-threatening chronic disease that prevents the heart from pumping sufficient levels of blood around the body. HF affects approximately 64 million people worldwide. HF remains as fatal as some of the most common cancers in both men (prostate and bladder cancers) and women (breast cancer).3 Chronic HF is the leading cause of hospitalisation for those over the age of 65 and represents a significant clinical and economic burden.4

AstraZeneca’s ambition is to be the leading company in HF. AstraZeneca is investing in multiple investigational therapies with diverse mechanisms of action to address the spectrum of patient need in this area.

ATTR-CM
Cardiomyopathy due to ATTR is caused by aging or genetic mutations resulting in misfolded TTR protein and accumulation as amyloid fibrils in the cardiac myocardium. In patients with ATTR-CM, both the mutant and wild type TTR protein builds up as fibrils in tissues, including the heart. The presence of TTR fibrils interferes with the normal functions of these tissues. As the TTR protein fibrils enlarge, more tissue damage occurs and the disease worsens, resulting in poor quality of life and eventually death.

Worldwide, there are an estimated 300,000-500,000 patients with ATTR-CM5,6; however, many of those patients remain undiagnosed.

NI006
NI006 is an investigational human monoclonal antibody that specifically targets misfolded transthyretin and is designed to directly address the pathology of ATTR-CM by enabling removal of amyloid fibril deposits in the heart, with the potential to treat patients with advanced ATTR-CM.

On March 1, 2022 Bicycle Therapeutics plc (NASDAQ: BCYC), a biotechnology company pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic peptide (Bicycle) technology, reported financial results for the fourth quarter and full year ended December 31, 2021, and provided recent corporate updates (Press release, Bicycle Therapeutics, MAR 1, 2022, View Source [SID1234609228]).

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"We are encouraged by the progress we continue to make across our oncology pipeline," said Kevin Lee, Ph.D., Chief Executive Officer of Bicycle Therapeutics. "As we previously reported, BT8009 and BT5528 have demonstrated anti-tumor activity in two tumor types, and we look forward to presenting interim results from our Phase I trial of BT8009 at a medical meeting and initiating the expansion cohorts in our clinical trial of BT5528 this year. We also are moving our Bicycle TICA programs forward, including BT7480, which entered the clinic in the fourth quarter of 2021. Our plans to advance our clinical programs, as well as to expand our discovery efforts and early development pipeline, are on track and are supported by a strong balance sheet, with sufficient cash to fund these initiatives and support operations through 2024."

Fourth Quarter 2021 and Recent Highlights

Announced Continued Progress in Ongoing Phase I/II Clinical Trials of BT8009, BT5528 and BT7480. In January 2022, Bicycle announced progress updates for its wholly owned oncology pipeline, including BTCs BT8009 and BT5528 and Bicycle TICA BT7480. In the ongoing Phase I portion of the Phase I/II clinical trial of BT8009, a second-generation BTC targeting Nectin-4, four out of 11 patients were previously reported to have a partial response under Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, including one out of four (25%) in the 2.5mg/m2 dose and three out of seven (43%) at the 5.0 mg/m2 cohorts. All four patients previously reported as responders have since received at least one subsequent scan, and all have been confirmed as ongoing RECIST 1.1 responses. One patient in the 5.0 mg/m2 cohort, who previously was reported to have a partial response with an 89% tumor reduction, has now received two subsequent scans, which each showed that total tumor volume has been reduced by 100%, constituting a confirmed complete response.

The Phase I/II trial of BT5528, Bicycle’s second-generation BTC targeting EphA2, is also ongoing, with initiation of expansion cohorts planned for this year, with an expected recommended Phase II dose of 6.5mg/m2 every-other-week.

Bicycle also initiated a Phase I clinical trial of BT7480, a novel, fully synthetic Bicycle TICA targeting Nectin-4 and agonizing CD137, in the fourth quarter of 2021, and dose escalation in that trial remains ongoing.
Announced Expansion of and Transition in Management Team. In January 2022, Michael Skynner, Ph.D., previously the company’s Chief Operating Officer (COO), was appointed to the newly created position of Chief Technology Officer, to focus on leading and overseeing the growth of Bicycle’s proprietary phage display discovery platform in oncology, as well as on creating innovative opportunities for the platform outside of oncology. Dr. Skynner joined the company in January 2016 as Vice President, Operations and Discovery and had served as COO since March 2018. Alistair Milnes, who served as the company’s Vice President, Human Resources and Communications since January 2021, has assumed the COO role. Mr. Milnes previously led human resources and communications at multinational energy and mineral companies. Both Dr. Skynner and Mr. Milnes are based in the United Kingdom.
Presented Preclinical BT7480 and BT7455 Data at the SITC (Free SITC Whitepaper) 36th Annual Meeting. In November 2021, Bicycle presented preclinical data for BT7480 and BT7455, an EphA2/CD137 Bicycle TICA. Results supported Bicycle’s decision to initiate a Phase I/II clinical trial of BT7480 and its prioritization of potential indications to target. Additionally, Bicycle has developed a pharmacokinetic/pharmacodynamic (PK/PD) modelling framework intended to predict preclinical biomarker level and tumor growth inhibition in response to changes in the BT7480 dose and dosing schedule. Bicycle found that plasma and tumor drug concentration levels may be associated with tumor growth inhibition.
Financial Results

Cash was $438.7 million as of December 31, 2021, compared to $136.0 million as of December 31, 2020. The net increase in cash is primarily due to financing activities during 2021, including net proceeds of $188.4 million from a public offering of Bicycle’s ADSs, net proceeds of $102.6 million from Bicycle’s at-the-market (ATM) offering program and net proceeds of $15.0 million from Bicycle’s debt facility with Hercules Capital, as well as $45.0 million received from Ionis Pharmaceuticals under the 2021 collaboration and license agreement, and $10.0 million received from Genentech for exercising an option to initiate an additional program under the 2020 collaboration agreement, offset by cash used for operating activities.
Research and development expenses were $13.0 million for the three months ended December 31, 2021 and $44.9 million for the year ended December 31, 2021, compared to $10.1 million for the three months ended December 31, 2020 and $33.1 million for the year ended December 31, 2020. The increase in expense of $2.9 million for the three months ended December 31, 2021 as compared to the same period in the prior year was primarily due to increased Bicycle TICA clinical program spend and other discovery and platform related expenses, as well as increased personnel related expenses, including $0.7 million of incremental non-cash share-based compensation expense. The increase in expense of $11.7 million for the year ended December 31, 2021 as compared to the same period in the prior year was primarily due to increased clinical program expenses for BT8009, Bicycle TICA and other discovery and platform related expenses and increased personnel-related expenses, including $2.4 million of incremental non-cash share-based compensation expense.
General and administrative expenses were $8.8 million for the three months ended December 31, 2021 and $32.4 million for the year ended December 31, 2021, compared to $10.9 million for the three months ended December 31, 2020 and $29.2 million for the year ended December 31, 2020. The decrease of $2.1 million for the three months ended December 31, 2021 as compared to the same period in the prior year was primarily due to the settlement and license agreement with Pepscan Systems B.V. ("Pepscan") entered into in November 2020, offset by increased costs to support operations as a public company and increased personnel-related costs, including $0.7 million of incremental non-cash share-based compensation expense. The increase of $3.2 million for the year ended December 31, 2021 as compared to the same period in the prior year was primarily due to increased personnel-related costs, including $3.2 million of incremental non-cash share-based compensation expense and increased costs to support operations as a public company, offset by a decrease in professional and consulting costs, and the settlement and license agreement with Pepscan entered into in November 2020.
Net loss was $18.0 million, or $(0.63) basic and diluted net loss per share, for the three months ended December 31, 2021, and net loss was $66.8 million, or $(2.67) basic and diluted net loss per share, for the year ended December 31, 2021, compared to net loss of $17.4 million, or $(0.83) basic and diluted net loss per share, for three months ended December 31, 2020, and net loss of $51.0 million, or $(2.66) basic and diluted net loss per share, for the year ended December 31, 2020.