On August 6, 2024 Agios Pharmaceuticals, Inc. (Nasdaq: AGIO), a leader in cellular metabolism and pyruvate kinase (PK) activation pioneering therapies for rare diseases, reported that the Company will receive a total of $1.1 billion in milestone payments following the U.S. Food and Drug Administration (FDA) approval of vorasidenib for adult and pediatric patients 12 years and older with Grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation following surgery, including biopsy, sub-total resection or gross total resection (Press release, Agios Pharmaceuticals, AUG 6, 2024, View Source [SID1234645404]). These payments include a $905 million payment from Royalty Pharma in connection with the vorasidenib royalty purchase agreement Agios announced in May 2024 and a $200 million payment from Servier in connection with Agios’ divestiture of its oncology business in 2021.

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"Today’s FDA approval of vorasidenib is the first approval for a Grade 2 glioma in over 20 years and highlights both the executional excellence of the Servier team and Agios’ expertise in discovering novel therapies for disease areas of high unmet need," said Cecilia Jones, chief financial officer at Agios. "The $1.1 billion in milestone payments triggered by today’s approval further strengthens our cash position, which we expect will provide us with the financial independence to prepare for potential PYRUKYND (mitapivat) launches in thalassemia in 2025 and sickle cell disease in 2026, as well as drive pipeline progress as we aim to build a multi-billion-dollar franchise."

Agios completed the sale of its oncology business to Servier on March 31, 2021. Under the terms of the agreement, Agios received $1.8 billion in upfront cash, an additional $200 million milestone payment upon FDA approval of vorasidenib, and 15% royalties on potential U.S. net sales of vorasidenib from the first commercial sale through loss of exclusivity. Agios had also retained rights to 5% royalties on U.S. net sales of Servier’s TIBSOVO (ivosidenib tablets), which it sold for a one-time payment of $131.8 million in 2022.

On May 28, 2024, Agios announced that the company agreed to sell its rights to its 15% royalty on potential U.S. net sales of vorasidenib to Royalty Pharma. Under the terms of the agreement, Agios receives an upfront payment of $905 million upon FDA approval of vorasidenib, and Royalty Pharma will receive the entirety of the 15% royalty on annual U.S. net sales of vorasidenib up to $1 billion and a 12% royalty on annual U.S. net sales greater than $1 billion. Agios will retain a 3% royalty on annual U.S. net sales greater than $1 billion.

On August 6, 2024 ADC Therapeutics SA (NYSE: ADCT), a commercial-stage global leader and pioneer in the field of antibody drug conjugates (ADCs), reported financial results for the second quarter ended June 30, 2024, and provided operational updates (Press release, ADC Therapeutics, AUG 6, 2024, View Source [SID1234645403]).

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"We continue to make progress on multiple fronts, including reaching a key milestone as ZYNLONTA achieves commercial profitability in the first half of the year. We are excited about the potential to further our growth as we move toward expanding into the second line setting of DLBCL and indolent lymphomas," said Ameet Mallik, Chief Executive Officer of ADC Therapeutics. "Additionally, we have now passed futility analysis with LOTIS-5 and expect to complete enrollment this year, while also planning to deliver updates on the LOTIS-7 trial and on ADCT-601 targeting AXL. With our expected cash runway extended into mid-2026, we are well positioned to execute our strategy and advance multiple value-generating catalysts before year-end."

Second Quarter 2024 Operational Updates & Recent Highlights

•ZYNLONTA: Reached commercial profitability in the first half of 2024, generating net product sales of $17.0 million in the second quarter of 2024, a 5% decrease as compared to revenue of $17.8 million in the first quarter of 2024. Demand was impacted in part by variability in ordering patterns in the second quarter.

•LOTIS-7: During the second quarter, the Company announced the completion of dose escalation in LOTIS-7, a Phase 1b open-label clinical trial evaluating ZYNLONTA in combination with bispecific antibodies glofitamab or mosunetuzumab in heavily pre-treated patients with relapsed/refractory B-cell non-Hodgkin lymphoma (r/r B-NHL). Enrollment in the Part 2 dose expansion is progressing and completion is expected by year-end. An update on safety and efficacy in evaluable patients is expected by year-end, with data on all patients anticipated in the first half of 2025.

•LOTIS-5: The Phase 3 confirmatory trial for ZYNLONTA in combination with rituximab in patients with 2L+ diffuse large B-cell lymphoma (DLBCL). An Independent Data Monitoring Committee (IDMC) conducted a prespecified interim analysis of unblinded data and has recommended that the trial continue as planned without modifications. Enrollment is nearing completion in the randomized portion of the trial with full enrollment expected before year-end 2024.

•Investigator-initiated trial in marginal zone lymphoma (MZL): Partial data from an investigator-initiated Phase 2 clinical trial evaluating ZYNLONTA for the treatment of relapsed/refractory (r/r) MZL were presented on May 6, 2024 at the Lymphoma Research Foundation’s 2024 Marginal Zone Lymphoma Scientific Workshop by the trial’s lead investigator. Initial data from the first 15 evaluable patients showed 13 achieved a complete response and 1 achieved a partial response. The multi-center study is designed to enroll 50 patients. Additional data publications and presentations at medical congresses are expected in 2024 or 2025.

•Investigator-initiated trial in follicular lymphoma (FL): The investigator-initiated Phase 2 clinical trial evaluating ZYNLONTA in combination with rituximab in patients with relapsed/refractory follicular lymphoma is currently being conducted at the Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine. Additional updates are expected at medical congresses in 2024 or 2025.

•ADCT-601 (targeting AXL): The Phase 1b trial in ADCT-601 targeting AXL continues enrolling patients in both the sarcoma and pancreatic cancer arms, optimizing dose and schedule. We plan to share an initial update from the Phase 1 trial in patients in the second half of 2024.

•Early-stage pipeline: Progress continues in the IND-enabling studies for the Company’s PSMA, NaPi2b and Claudin-6 targeting ADCs. ASCT2 targeting ADC is in drug candidate selection stage and is still on track to complete this year. The Company has selected one target to move forward toward IND which we expect to disclose in 2025.
Second Quarter and First Half 2024 Financial Results

•Cash and cash equivalents: As of June 30, 2024, cash and cash equivalents were $300.1 million, compared to $278.6 million as of December 31, 2023. In May 2024 the Company completed an underwritten offering resulting in net proceeds of approximately $97.4 million, extending the expected cash runway into mid-2026.

•Product Revenues: Net product revenues were $17.0 million for the second quarter ended June 30, 2024 and $34.9 million for the first six months of 2024 as compared to $19.2 million and $38.2 million for the same periods in 2023. The quarter-over-quarter decrease is primarily due to lower sales volume, partially offset by a higher price. The year-to-date decrease is primarily due to lower sales volumes, as well as higher gross-to-net deductions primarily due to the discarded drug rebate accrual partially offset by a higher price.

•Research and Development (R&D) Expense: R&D expense was $24.3 million and $50.0 million for the three and six months ended June 30, 2024, respectively. This compares to R&D expense of $31.3 million and $69.7 million for the same periods in 2023. The decrease is due primarily to implementation of productivity initiatives and focused investment in prioritized development programs.

•Selling and Marketing (S&M) Expense: S&M expense was $10.7 million and $22.1 million for the three and six months ended June 30, 2024, respectively. This compares to S&M expense of $14.5 million and $29.8 million for the same periods in 2023. The decrease in S&M expense was primarily due to lower marketing and advertising costs and personnel related expenses.

•General & Administrative (G&A) Expense: G&A expense was $10.2 million and $22.3 million for the three and six months ended June 30, 2024, respectively. This compares to G&A expense of $12.0 million and $27.5 million for the same periods in 2023. The quarter-over-quarter decrease in G&A expense was primarily related to lower legal and audit fees, insurance and IT expenses while the year-to-date decrease was primarily related to lower insurance and IT expenses, partially offset by higher legal and audit fees.

•Net Loss: Net loss for the quarter ended June 30, 2024 was $36.5 million, or a net loss of $0.38 per basic and diluted share, as compared to net loss of $48.9 million, or a net loss of $0.60 per basic and diluted share for the same period in 2023. Net loss for the six months ended June 30, 2024 was $83.2 million, or a net loss of $0.93 per basic and diluted share, as compared to net loss of $108.3 million, or a net loss of $1.33 per basic and diluted share for the six months ended June 30, 2023. The decrease is primarily due to lower operating expenses.

•Adjusted Net Loss: Adjusted net loss, which is a non-GAAP financial measure, was $24.4 million, or an adjusted net loss of $0.25 per basic and diluted share for the quarter ended June 30, 2024 as compared to adjusted net loss of $32.1 million, or $0.39 per basic and diluted share, for the same period in 2023. Adjusted net loss for the six months ended June 30, 2024 was $55.5 million, or an adjusted net loss of $0.62 per basic and diluted share, as compared to net loss of $73.9 million, or an adjusted net loss of $0.91 per basic and diluted share for the six months ended June 30, 2023. The decrease in adjusted net loss is primarily attributable to lower operating expenses.

Conference Call Details

ADC Therapeutics management will host a conference call and live audio webcast to discuss second quarter 2024 financial results and provide a company update today at 8:30 a.m. Eastern Time. To access the conference call, please register here. Registrants will receive the dial-in number and unique PIN. It is recommended that you join 10 minutes before the event, though you may pre-register at any time. A live webcast of the call will be available under "Events & Presentations" in the Investors section of the ADC Therapeutics website at ir.adctherapeutics.com. The archived webcast will be available for 30 days following the call.

About ZYNLONTA

ZYNLONTA is a CD19-directed antibody drug conjugate (ADC). Once bound to a CD19-expressing cell, ZYNLONTA is internalized by the cell, where enzymes release a pyrrolobenzodiazepine (PBD) payload. The potent payload binds to DNA minor groove with little distortion, remaining less visible to DNA repair mechanisms. This ultimately results in cell cycle arrest and tumor cell death.

The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have approved ZYNLONTA (loncastuximab tesirine-lpyl) for the treatment of adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), DLBCL arising from low-grade lymphoma and also high-grade B-cell lymphoma. The trial included a broad spectrum of heavily pre-treated patients (median three prior lines of therapy) with difficult-to-treat disease, including patients who did not respond to first-line therapy, patients refractory to all prior lines of therapy, patients with double/triple hit genetics and patients who had stem cell transplant and CAR-T therapy prior to their treatment with ZYNLONTA. This indication is approved by the FDA under accelerated approval and in the European Union under conditional approval based on overall response rate and continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Please see full prescribing information including important safety information about ZYNLONTA at www.ZYNLONTA.com.

ZYNLONTA is also being evaluated as a therapeutic option in combination studies in other B-cell malignancies and earlier lines of therapy.

On August 6, 2024 Sysmex Corporation (HQ: Kobe, Japan; President: Kaoru Asano) reported that it has expanded its strategic Alliance Agreement with QIAGEN N.V. (HQ: Venlo, The Netherlands; CEO: Thierry Bernard) to deepen their collaboration in genetic testing, including research and development, production, clinical development, and sales-marketing (Press release, Sysmex, AUG 6, 2024, View Source [SID1234645391]).

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Sysmex and QIAGEN have built a successful partnership since the initial collaboration back in 2013 and agreed to expand it to include a strategic alliance for companion diagnostics1 in 2021. As part of the newly expanded collaboration, both companies will further combine their respective products and strengths in genetic testing to deliver high-value products to their global customers.

Sysmex will implement QIAGEN’s assay to be used for clinical trials that QIAGEN provides to pharmaceutical companies and research institutions at Sysmex’s global network laboratories (Sysmex Inostics, Inc. CLIA lab2, Sysmex Research and Development Center and Sysmex affiliated company, RIKEN GENESIS Co., Ltd. (HQ: Shinagawa-ku, Tokyo; President and CEO: Kenji Iwakabe) and support QIAGEN’s global services.

For more than 50 years, Sysmex has enhanced its global presence within the in vitro diagnostics field by evolving its genetic testing portfolio. One of the ways is by bringing personalized medicine to patients and healthcare professionals through product development using liquid biopsy3 technology. Sysmex has built a global sales and services network that utilizes its world-class laboratories in Japan and the United States. Sysmex intends to accelerate the creation of high-value testing and develop diagnostic technologies further.

QIAGEN is a pioneer in precision medicine4 and the leader in collaborating with pharmaceutical and biotechnology companies to develop companion diagnostics. These can detect genetic abnormalities to provide insights that guide clinical decision-making about treatments. From polymerase chain reaction (PCR), multiplex PCR, digital PCR (dPCR)5 to next-generation sequencing (NGS)6, QIAGEN offers an unmatched breadth of technologies, which means it can tailor products to the needs of pharmaceutical companies. The company has master collaboration agreements to develop and commercialize companion diagnostics with more than 30 global pharma companies worldwide.

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.