On May 5, 2020 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 that the first patient has been dosed in a Phase I dose escalation of BT5528 in combination with nivolumab (Press release, Bicycle Therapeutics, MAY 5, 2020, View Source [SID1234556996]). The Phase I trial includes both a monotherapy arm as well as a combination arm. Per protocol, the monotherapy arm began first, with the first patient dosed in the fourth quarter of 2019, and dosing in both arms is now underway. In the monotherapy arm, doses administered to date appear well-tolerated as the escalation continues toward clinically relevant doses. BT5528 is a Bicycle Toxin Conjugate (BTC) that targets EphA2, an antigen believed to be overexpressed in tumor types with high unmet need and a target for which antibody-based approaches have been unsuccessful to date.

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"We have been able to move the Phase I/II trial forward quickly by leveraging learnings from the ongoing clinical development of our first generation, pathfinder BTC, BT1718, which is sponsored by Cancer Research UK. We are very pleased with the progress we’ve made thus far in the BT5528 trial, which is intended to demonstrate the potential of Bicycles as a new therapeutic modality capable of addressing therapeutic needs that can’t be reached by conventional treatment options," said Kevin Lee, Ph.D., Chief Executive Officer of Bicycle Therapeutics. "Doses of BT5528 administered to date continue to be well-tolerated, suggesting that BT5528 may circumvent limitations that have caused prior antibody drug conjugate, or ADC, approaches that target EphA2 to fail. Because we believe BTCs may result in improved safety and efficacy over ADCs, in part through more selective delivery of toxin to tumor, we similarly believe that our approach may improve on anti-tumor activity and immunologic effects observed for ADCs in combination with checkpoint inhibitors."

The Phase I/II multi-center, open-label trial of BT5528 is currently enrolling patients with advanced solid tumors in indications associated with EphA2 expression. The Phase I dose escalations of BT5528 as a monotherapy and in combination with nivolumab are primarily designed to assess safety and tolerability and to determine a recommended Phase II dose (RP2D). Following selection of an RP2D, we expect to initiate a Phase II dose expansion portion with the primary objective of evaluating the clinical activity of BT5528.

On May 5, 2020 TG Therapeutics, Inc. (NASDAQ: TGTX), reported positive topline results from the global UNITY-CLL Phase 3 trial evaluating the combination of umbralisib plus ublituximab (U2) compared to obinutuzumab plus chlorambucil in patients with previously untreated and relapsed/refractory chronic lymphocytic leukemia (CLL) (Press release, TG Therapeutics, MAY 5, 2020, View Source [SID1234556995]). The trial met its primary endpoint at a prespecified interim analysis demonstrating a statistically significant improvement in progression-free survival (PFS) (p<.0001), and will be stopped early for superior efficacy. PFS was assessed by an Independent Review Committee (IRC), and benefit was also seen across both previously untreated and relapsed/refractory patient populations. The UNITY-CLL Phase 3 trial is being conducted under Special Protocol Assessment (SPA) agreement with the U.S. Food and Drug Administration (FDA).

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An independent data safety monitoring board (DSMB) conducted the interim analysis and made the recommendation to stop the trial early based on the positive results. Secondary endpoints, including safety, were not reviewed by the DSMB at this meeting. Data from this study is intended to support a regulatory submission targeted by year-end 2020 for U2 in both previously untreated and relapsed/refractory CLL patients and will be submitted for presentation at a future medical conference.

Michael S. Weiss, Executive Chairman and Chief Executive Officer of TG Therapeutics stated, "We could not be more excited to share the positive topline results. As a company we have been focused on developing the best possible treatments, including novel combinations for individuals with B-cell diseases, and today’s announcement truly marks the culmination of years of hard work and a major step forward in our mission. This outcome sets the stage for the potential approval of U2 as a novel, chemotherapy-free, treatment regimen for patients with CLL, whether they have relapsed from or are refractory to a prior therapy or have never been treated before." Mr. Weiss continued, "We are extremely pleased with the performance of U2 in this study and very happy we were able to stop the study at this interim analysis due to the superior efficacy observed. We want to thank the patients, their families, and the doctors and research teams who participated in this trial, as well as our extraordinary team at TG who made this study a success. We look forward to submitting this data to the FDA and presenting the full results at a major medical meeting targeted by year-end 2020."

John Gribben, MD, DSc, FRCP, FRCPath, FMed Sci, Professor of Medical Oncology, Barts Cancer Institute, London, UK, and Global Study Chair for the UNITY-CLL study stated, "It’s extremely gratifying to see positive results for this important trial exploring the combination of umbralisib and ublituximab in patients with both front-line and relapsed/refractory CLL. Today’s outcome marks the first successful Phase 3 trial of a PI3K delta-based regimen in a CLL patient population that included previously untreated patients." Dr. Gribben continued, "CLL remains incurable and new treatment options are still very much needed, particularly those that provide a differentiated mechanism and safety profile from our currently available treatment options."

ABOUT UNITY-CLL PHASE 3 TRIAL
UNITY-CLL is a global Phase 3 randomized controlled clinical trial comparing the combination of ublituximab plus umbralisib, or U2, to an active control arm of obinutuzumab plus chlorambucil in patients with both treatment-naïve and relapsed or refractory chronic lymphocytic leukemia (CLL). The trial randomized patients into four treatment arms: ublituximab single agent, umbralisib single agent, ublituximab plus umbralisib and an active control arm of obinutuzumab plus chlorambucil. A prespecified analysis was conducted to assess the contribution of ublituximab and umbralisib in the U2 combination arm and allowed for the termination of the single agent arms. Accordingly, the UNITY-CLL Phase 3 trial continued enrollment in a 1:1 ratio into the two combination arms: the investigational arm of U2 and the control arm of obinutuzumab plus chlorambucil. Full enrollment into the UNITY-CLL Phase 3 trial completed in October of 2017 with approximately 420 subjects enrolled to the two combinations arms. This trial enrolled approximately 60% treatment-naïve CLL patients and 40% relapsed or refractory CLL patients. The primary endpoint for this study was superior Progression Free Survival (PFS) for the U2 combination compared to the control arm to support the submission for full approval of the U2 combination in CLL. The UNITY-CLL Phase 3 trial is being conducted under Special Protocol Assessment (SPA) agreement with the U.S. Food and Drug Administration (FDA).

CONFERENCE CALL INFORMATION
The Company will host a conference call today, Tuesday, May 5, 2020 at 8:30 AM ET to discuss the UNITY-CLL Phase 3 Trial. In order to participate in the conference call, please call 1-877-407-8029 (U.S.), 1-201-689-8029 (outside the U.S.), Conference Title: TG Therapeutics.

A live webcast of this presentation will be available on the Events page, located within the Investors & Media section, of the Company’s website at www.tgtherapeutics.com. An audio recording of the conference call will also be available for replay at www.tgtherapeutics.com, for a period of 30 days after the call.

ABOUT CHRONIC LYMPHOCYTIC LEUKEMIA
Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia, and in 2020 it is estimated there will be more than 20,000 new cases of CLL diagnosed in the United States1. Although signs of CLL may disappear for a period of time after initial treatment, the disease is considered incurable and many people will require additional treatment due to the return of malignant cells.

On May 5, 2020 Crescendo Biologics Ltd (Crescendo), the developer of novel, targeted, T cell enhancing therapeutics, and Cancer Research UK, the world’s largest independent funder of cancer research, reported a Clinical Development Partnership to progress one of Crescendo’s novel bispecific Humabody immunotherapies, CB213, into clinical trials targeting cancers of high unmet medical need (Press release, Crescendo Biologics, MAY 5, 2020, View Source [SID1234556987]).

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Under the terms of the agreement, Cancer Research UK’s Centre for Drug Development will sponsor and fund a future Phase I clinical trial for CB213, in patients with solid tumours. Crescendo retains the right to further develop the CB213 immunotherapy programme, by licensing the results of the trial from Cancer Research UK for an undisclosed amount, success-based milestones and royalty payments.

CB213, a novel bispecific PD-1 x LAG-3 antagonist, is a next-generation checkpoint inhibitor, which has been designed to deliver safer, more effective therapeutic intervention in patients with cancers resistant or refractory to PD-1 blockade alone. In preclinical testing, CB213 has demonstrated potent dual checkpoint blockade and the ability to enhance the activity of dysfunctional patient-derived T cells.

Theodora Harold, CEO of Crescendo Biologics, said:

"We are delighted to be collaborating with the world-renowned institution of Cancer Research UK to advance our CB213 programme. Cancer Research UK’s endorsement of our science demonstrates important validation of our Humabody technology and provides an opportunity to accelerate our CB213 programme into the clinic. CB213 is a promising therapeutic candidate for treating patients with solid tumours, where conventional or combination immunotherapies have failed. We look forward to working with the team at Cancer Research UK’s Centre for Drug Development."

Dr Nigel Blackburn, Cancer Research UK’s Director of Drug Development, said:

"We’re proud to be working with Crescendo at the forefront of oncology innovation and cancer drug development. By combining our expertise, we’re able to accelerate the development of this promising experimental treatment, bringing it to patients with cancers that are hard to treat."

On May 4, 2020 Domain Therapeutics, a biopharmaceutical company specializing in the discovery and development of new drugs targeting G Protein-Coupled Receptors (GPCRs) in immuno-oncology, neurology and rare diseases, reported that the decision of Merck KGaA, Darmstadt, Germany, to enter into a regulatory phase of drug development with its candidate, triggers an undisclosed milestone payment to Domain Therapeutics (Press release, Domain Therapeutics, MAY 4, 2020, View Source [SID1234606731]).

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The candidate was identified during a collaboration with Merck KGaA, Darmstadt, Germany, that was initiated in 2017, making Domain Therapeutics eligible for more than €240 million ($261M) in development milestones, as well as undisclosed royalties. The compound is an orally available small molecule antagonist of adenosine receptors. It fulfils all the criteria defined by Merck KGaA, Darmstadt, Germany, to become a valuable drug candidate and to be developed as a differentiated immunotherapeutic agent in multiple cancers.

The adenosine receptor antagonist program brought to the collaboration by Domain Therapeutics was the first asset from its immuno-oncology franchise, which has significantly expanded over the years. Today, the company has other assets from hit-to-lead to candidate stage and has secured exclusive access to a target validation approach to identify GPCR modulation in the immuno-oncology field.

"This new adenosine receptor antagonist is one of the strategic assets in our immuno-oncology pipeline," said Joern-Peter Halle, senior vice president, head of immuno-oncology research at Merck KGaA, Darmstadt, Germany. "It results from a successful and productive collaboration between the Domain and Merck KGaA, Darmstadt, Germany teams. We are eager to see the compound progressing through regulatory development and entering the clinic for the benefit of cancer patients."

"We are delighted to have contributed to the strengthening of Merck KGaA, Darmstadt, Germany’s portfolio in immuno-oncology with a new adenosine receptor antagonist," said Pascal Neuville, CEO of Domain Therapeutics. "This is a great achievement for Domain. It illustrates its capacity to discover and deliver valuable clinical candidates and highlights Domain’s innovation capacity in immunotherapies."

About adenosine receptor antagonists in immuno-oncology
Adenosine is a powerful immunosuppressive substance produced inside tumors as a result of rapid cancer cell turnover. In some cases, it is responsible for resistance to certain anti-tumor interventions, such as chemotherapy and radiation. The adenosine receptors, expressed on the surface of immune cells, mediate the immunosuppressive effects of adenosine. The adenosine-driven impairment of tumor-infiltrating lymphocytes (mainly CD8+ T cells and NK cells) and myeloid cells (dendritic cells, macrophages), mediated by adenosine receptors, requires the development of specific inhibitors. For the last few years, the pharma industry has been investigating the benefit of combining adenosine receptor antagonists with ICI in order to decrease adenosine-mediated resistance and restore ICI antitumor activity.

On May 4, 2020 Turning Point Therapeutics, Inc. (NASDAQ: TPTX), a precision oncology company developing next-generation therapies that target genetic drivers of cancer, reported that it will report first quarter financial results following the close of U.S. financial markets on May 12 and host a conference call at 1:30 p.m. PT/4:30 p.m. ET to discuss the results and provide operational updates (Press release, Turning Point Therapeutics, MAY 4, 2020, View Source [SID1234564375]). President and CEO Athena Countouriotis, M.D., will host the call, which will include a question and answer session.

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The update will be accessible via audio webcast through the "Investors" section of www.tptherapeutics.com or by dialing (877) 388-2118 (in the United States) or (470) 495-9489 (outside the U.S.) using conference ID 6135289. A replay will be available through the "Investors" section of www.tptherapeutics.com.