On August 6, 2024 Daiichi Sankyo (TSE: 4568) and Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported the companies have expanded their existing global co-development and co-commercialization agreement for three investigational DXd antibody drug conjugates to include Merck’s MK-6070, an investigational delta-like ligand 3 (DLL3) targeting T-cell engager (Press release, Daiichi Sankyo, AUG 6, 2024, https://daiichisankyo.us/press-releases/-/article/daiichi-sankyo-and-merck-enter-into-global-development-and-commercialization-agreement-for-mk-6070 [SID1234645358]). The companies will jointly develop and commercialize MK-6070 worldwide, except in Japan where Merck will maintain exclusive rights. Merck will be solely responsible for manufacturing and supply for MK-6070.

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MK-6070 is a T-cell engager targeting DLL3, an inhibitory canonical Notch ligand that is expressed at high levels in small cell lung cancer (SCLC) and neuroendocrine tumors, currently being evaluated in a phase 1/2 clinical trial. The companies are planning to evaluate MK-6070 in combination with ifinatamab deruxtecan (I-DXd) in certain patients with SCLC, as well as other potential combinations. Merck obtained MK-6070 through its acquisition of Harpoon Therapeutics.

"Expanding our oncology pipeline with a DLL3 T-cell engager further supports Daiichi Sankyo’s strategy to create new standards of care for patients with cancer worldwide," said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. "We look forward to continuing our relationship with Merck with the addition of MK-6070 as it provides potential synergies with our established antibody drug conjugate collaboration, particularly ifinatamab deruxtecan, and demonstrates our shared commitment to advancing new medicines for patients."

"Small cell lung cancer is an aggressive, fast-growing form of lung cancer and new treatment approaches are urgently needed," said Dean Y. Li, MD, PhD, President, Merck Research Laboratories. "We are pleased to build upon our collaboration with Daiichi Sankyo and look forward to evaluating the combination of MK-6070 and ifinatamab deruxtecan as a novel two-pronged approach targeting the underlying biology of small cell lung cancer along with other forms of cancer."

Financial Highlights
Under the terms of the agreement, Merck will receive an upfront cash payment of $170 million and has also satisfied a contingent quid obligation from the original collaboration agreement. The companies will share R&D and commercialization expenses as well as profits worldwide, except for Japan where Merck retains exclusive rights and Daiichi Sankyo receives a royalty based on sales. R&D expenses related to MK-6070 in combination with ifinatamab deruxtecan will be shared in a manner consistent with the original agreement for ifinatamab deruxtecan. Merck will generally record sales for MK-6070 worldwide.

About DLL3
Delta-like ligand 3 (DLL3), a Notch inhibitory ligand, is highly expressed on SCLC and other neuroendocrine tumors such as melanoma, small cell bladder cancer and metastatic castration resistant prostate cancer and is minimally expressed in normal tissues.1 DLL3 is a promising therapeutic target where multiple treatment approaches are being explored.1, 2

About MK-6070
MK-6070 is an investigational DLL3 directed tri-specific T-cell engager currently being evaluated in a phase 1/2 clinical trial as a monotherapy in certain patients with advanced cancers associated with expression of DLL3 and in combination with atezolizumab in certain patients with SCLC. The U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation to MK-6070 for the treatment of SCLC in March 2022.

About the Daiichi Sankyo and Merck Collaboration
Daiichi Sankyo and Merck (known as MSD outside of the United States and Canada) entered into a global collaboration in October 2023 to jointly develop and commercialize patritumab deruxtecan (HER3-DXd), ifinatamab deruxtecan (I-DXd) and raludotatug deruxtecan (R-DXd), except in Japan where Daiichi Sankyo will maintain exclusive rights. Daiichi Sankyo is solely responsible for manufacturing and supply.

On August 5, 2024 Genor Biopharma (Stock code: 6998.HK) reported that the company had entered into a licensing agreement and a stock purchase agreement with TRC 2004.Under the License Agreement, Genor Biopharma has agreed, among others, to grant the Licensee an exclusive worldwide license to develop, use, manufacture, commercialize and otherwise exploit GB261 (CD20/CD3, BsAb) , excluding mainland China, Hong Kong, Macau and Taiwan (Press release, , AUG 5, 2024, View Source [SID1234648372]).

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According to the agreement, Genor Biopharma shall receive:

a significant equity participation in the Licensee;
a double digit million US dollars upfront payment;
up to 443 million US dollars in milestone payments;
tiered single to double digits royalty payments on net sales.

GB261 is a novel differentiated CD20 / CD3 bi-specific T-Cell Engager with ultra-low affinity to bind CD3 and has Fc-enabled functions (ADCC and CDC). GB261 has previously completed a Phase Ph1/2 multi-center study of B-NHL (DLBCL and FL) in China and Australia, which demonstrated promising efficacy and a favorable safety profile. Meanwhile, GB261 has been shown to significantly reduce cytokine release (CRS) compared with bi-specifics in the same class.

The properties of GB261 make it a very promising B-cell depletion agent and its indication potential extends beyond oncology and is also applicable to various immunological and autoimmune indications where there is a large unmet medical need in patients.

On August 5, 2024 BioNTech reported the Quarterly Report of BioNTech SE for the three and six months ended June 30, 2024 (Press release, BioNTech, AUG 5, 2024, View Source [SID1234645696]).

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On August 5, 2024 Tubulis reported that Fierce Biotech has named the company as one of 2024’s "Fierce 15" biotechnology companies (Press release, Tubulis, AUG 5, 2024, View Source [SID1234645356]). The annual special report features the most innovative and promising biotechnology companies in the industry.

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"Being selected for this prestigious industry award is an important recognition of our leadership position in the ADC space as well as the potential of our unique approach to ADC development. It also is a great reward for all the hard work our team has been putting into driving innovation and realizing our mission of improving the outcomes for cancer patients. I specifically would like to thank every team member and our Board for their contributions," said Dominik Schumacher, CEO at Tubulis. "2024 is a pivotal year for us and we are committed to further building on this momentum to push the boundaries of ADCs and unlock their full therapeutic potential."

Tubulis was established with the goal of maximizing the overall performance of ADCs by addressing the main bottlenecks in the field through innovation in all aspects of ADC development. The company has created a unique suite of technologies that combine a diverse range of targeting molecules, innovative payloads, and proprietary conjugation technologies to deliver revolutionary ADCs with superior biophysical properties and durable anti-tumor effects. Based on differentiated preclinical results recently presented at AACR (Free AACR Whitepaper) and backed by an upsized €128 million Series B2 financing in March, the company is now translating the durable efficacy of its lead candidates, TUB-030 and TUB-040, into the clinic. In June, the first patient was dosed with TUB-040 in a Phase I/IIa study (NAPISTAR 1-01, NCT06303505) to investigate its safety, pharmacokinetics and efficacy in patients with platinum-resistant high-grade ovarian cancer (PROC) and relapsed/refractory adenocarcinoma non-small cell lung cancer (NSCLC), who have exhausted other available treatment options. Shortly afterwards, the candidate was granted Fast Track designation by the U.S. Food and Drug Administration ("FDA") for the treatment of patients with PROC.

"For the past 22 years, we have evaluated hundreds of companies for inclusion in the ‘Fierce 15’ special report. Our selection process considers various factors, including technological robustness, strategic partnerships, venture support and market positioning," said Ayla Ellison, Editor-in-Chief, Fierce Life Sciences and Healthcare. "This report highlights innovation and creativity amid intense competition."

On August 5, 2024 Nuvation Bio Inc. (NYSE: NUVB), a late clinical-stage, global biopharmaceutical company tackling some of the greatest unmet needs in oncology, reported financial results for the second quarter ended June 30, 2024, and provided a business update (Press release, Nuvation Bio, AUG 5, 2024, View Source [SID1234645355]).

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"In the second quarter, we were pleased to share data at ASCO (Free ASCO Whitepaper) from TRUST-I, the pivotal study of taletrectinib in China, which although immature due to an early data cutoff, demonstrated taletrectinib’s efficacy, durability, and safety profiles. At WCLC, we will be presenting data from TRUST-II, the global, pivotal Phase 2 study of taletrectinib, while at ESMO (Free ESMO Whitepaper) we will present more mature and comprehensive taletrectinib data, including pooled efficacy and safety data from both pivotal TRUST-I and TRUST-II studies. The ESMO (Free ESMO Whitepaper) data set will be used to support our planned NDA filing in the U.S. and, assuming regulatory approval, will position us to commercialize taletrectinib in 2025," said David Hung, M.D., Founder, President, and Chief Executive Officer of Nuvation Bio. "We are also progressing the global Phase 2 study of safusidenib and continuing to dose escalate in a Phase 1/2 study of our first clinical-stage drug-drug conjugate, NUV-1511. As we focus on our late-stage pipeline and prepare to potentially bring taletrectinib to patients in the U.S. in 2025, we have decided not to initiate a Phase 2 study of NUV-868 in the solid tumor indications studied to date. This decision comes after careful review of the data generated in the Phase 1 monotherapy study and Phase 1b study of NUV-868 in combination with olaparib or enzalutamide. We are exploring next steps for NUV-868 in new indications and will share updates as available. We are proud of Nuvation Bio’s transformational momentum in the first half of this year and look forward to building upon it as we tackle some of the greatest unmet needs in oncology."

Recent Pipeline Updates:

Taletrectinib, ROS1 inhibitor: Advanced ROS1-positive NSCLC

Latest data from the Phase 2 TRUST-I clinical study evaluating taletrectinib in patients in China with advanced ROS1-positive NSCLC was published in the Journal of Clinical Oncology and presented at the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting.
Latest pooled data from the pivotal Phase 2 TRUST-I and TRUST-II studies to be presented at the ESMO (Free ESMO Whitepaper) Congress 2024 in September, which will support the Company’s planned NDA in the U.S.
Latest data from the global, pivotal Phase 2 TRUST-II study to be presented at the WCLC in September.
Granted Orphan Drug Designation by the U.S. FDA for the treatment of ROS1-positive NSCLC and other NSCLC indications.
Safusidenib, mIDH1 inhibitor: Diffuse IDH1-mutant glioma

Global phase 2 study of safusidenib for treatment of patients with diffuse IDH1-mutant glioma remains ongoing.
NUV-1511, drug-drug conjugate (DDC): Advanced solid tumors

Phase 1/2 dose escalation study of NUV-1511 for the treatment of patients with various advanced solid tumors remains ongoing.
NUV-868, BD2-selective BET inhibitor: Advanced solid tumors

Concluded the Phase 1b dose escalation study of NUV-868 in combination with olaparib for the treatment of patients with ovarian cancer, pancreatic cancer, metastatic castration-resistant prostate cancer (mCRPC), triple negative breast cancer, and other solid tumors, and in combination with enzalutamide for the treatment of patients with mCRPC.
Completed an internal analysis of efficacy and safety data collected from the Phase 1 monotherapy and Phase 1b combination studies of NUV-868. Following this analysis, Nuvation Bio decided not to initiate a Phase 2 study of NUV-868 as a monotherapy or in combination with olaparib or enzalutamide in the advanced solid tumor indications that were part of the Phase 1 and Phase 1b study designs. The Company is evaluating next steps for the NUV-868 program, including further development in combination with approved products for indications in which BD2-selective BET inhibitors may improve outcomes for patients.
Second Quarter 2024 Financial Results

As of June 30, 2024, Nuvation Bio had cash, cash equivalents and marketable securities of $577.2 million.

For the three months ended June 30, 2024, research and development expenses were $29.2 million, compared to $18.6 million for the three months ended June 30, 2023. The increase was primarily due to a $5.9 million increase in personnel-related costs driven by the acquisition of AnHeart Therapeutics, Ltd. (AnHeart), stock-based compensation and other benefits and a $4.7 million increase in third-party costs related to research services and drug manufacturing as a result of clinical study expense for taletrectinib.

On April 9, 2024, as a result of the acquisition of AnHeart, Nuvation Bio recorded a $425.1 million charge representing an acquired in-process research and development asset with no alternative future use in acquired in-process research and development expenses.

For the three months ended June 30, 2024, general and administrative expenses were $16.1 million, compared to $7.5 million for the three months ended June 30, 2023. The increase was due to a $3.9 million increase in personnel-related costs as a result of the acquisition of AnHeart, a $1.1 million increase in professional fees, a $1.2 million increase in marketing expense, a $0.8 million increase in legal fees, a $0.2 million increase in occupancy expense, a $0.2 million increase in foreign currency impact, and a $1.4 million increase in miscellaneous expense offset by a $0.2 million decrease in insurance expense.

For the three months ended June 30, 2024, Nuvation Bio reported a net loss of $462.5 million, or $(1.89) per share. This compares to a net loss of $20.6 million, or $(0.09) per share, for the comparable period in 2023.

About Taletrectinib

Taletrectinib is an oral, potent, central nervous system-active, selective, next-generation ROS1 inhibitor specifically designed for the treatment of patients with ROS1-positive non-small cell lung cancer (NSCLC). Taletrectinib is being evaluated for the treatment of patients with advanced ROS1-positive NSCLC in two Phase 2 single-arm pivotal studies: TRUST-I (NCT04395677) in China, and TRUST-II (NCT04919811), a global study. Taletrectinib has been granted Orphan Drug Designation by the U.S. FDA for the treatment of patients with ROS1-positive NSCLC and Breakthrough Therapy Designations by both the U.S. FDA and China’s National Medical Products Administration (NMPA) for the treatment of patients with advanced or metastatic ROS1-positive NSCLC. Based on results of the TRUST-I clinical study, China’s NMPA has accepted and granted Priority Review Designations to New Drug Applications for taletrectinib for the treatment of adult patients with locally advanced or metastatic ROS1-positive NSCLC who either have or have not previously been treated with ROS1 tyrosine kinase inhibitors.