On December 2, 2024 Merus N.V. (Nasdaq: MRUS) (Merus, the Company, we, or our), a clinical-stage oncology company developing innovative, full-length multispecific antibodies (Biclonics and Triclonics) and Partner Therapeutics, Inc. (PTx), a private, fully-integrated biotechnology company with a focus in hematology and oncology, reported they have entered into an agreement in which Merus has exclusively licensed to PTx the right to commercialize zenocutuzumab (Zeno) for the treatment of NRG1 fusion-positive (NRG1+) cancer in the United States (U.S.).

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"We are thrilled to work with the seasoned team at PTx to advance our mission to bring Zeno to patients with NRG1+ cancer," said Shannon Campbell, Chief Commercial Officer of Merus. "We believe PTx is an ideal partner to support Zeno given their oncology commercialization expertise and executive team’s deep understanding and experience with NRG1+ cancer."

"Zeno has the potential to be the first and only targeted therapy for patients with NRG1+ non-small cell lung and pancreatic cancer, and may offer a substantial improvement over currently available therapies," said Sarah Kurz, President and Chief Operating Officer of PTx. " We are grateful to Merus for their development of Zeno, which has the potential to fill an unmet medical need for these patients."

Under the terms of the agreement, following a specified transition period, PTx will assume full rights to U.S. commercialization of Zeno for the treatment of NRG1+ cancer. In exchange for the rights granted under the license agreement, Merus will receive an upfront payment and is eligible to receive milestones and high single digit to low double-digit royalty payments based on the annual net sales of Zeno in NRG1+ cancer in the U.S. for any potential future sales.

A Biologics License Application for Zeno is currently under review by the U.S. Food and Drug Administration for the treatment of patients with previously treated NRG1+ non-small cell lung cancer and pancreatic cancer.

(Press release, Merus, DEC 2, 2024, View Source [SID1234661244])

On December 2, 2024 Olema Pharmaceuticals, Inc. ("Olema" or "Olema Oncology", Nasdaq: OLMA), a clinical-stage biopharmaceutical company focused on the discovery, development, and commercialization of targeted therapies for breast cancer and beyond, reported a new clinical trial collaboration and supply agreement with Novartis in frontline metastatic breast cancer (Press release, Olema Oncology, DEC 2, 2024, View Source [SID1234648721]). Olema has also entered into a securities purchase agreement for the private placement of approximately $250.0 million of common stock and pre-funded warrants to purchase common stock with new and existing institutional and accredited investors (the "Private Placement").

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"We are now fully enabled to initiate our planned pivotal Phase 3 clinical trial, OPERA-02, for palazestrant in combination with ribociclib in frontline ER+/HER2- metastatic breast cancer. Our new agreement with Novartis, which includes sufficient ribociclib drug supply for the planned approximately 1,000 patient trial, is a major milestone. When combined with our Private Placement of $250.0 million of common stock and pre-funded warrants with high-quality, long-term investors, Olema now expects to have the necessary resources to execute OPERA-02, the Phase 1/2 study of OP-3136, and the ongoing Phase 3 OPERA-01 monotherapy trial," said Sean P. Bohen, M.D., Ph.D., President and Chief Executive Officer of Olema Oncology. "We remain on track to share topline data from OPERA-01 in 2026 and we are excited to present our latest data from the ongoing Phase 1b/2 study of palazestrant in combination with ribociclib at the San Antonio Breast Cancer Symposium (SABCS) next week."

New Clinical Trial Collaboration and Supply Agreement Enables Phase 3 OPERA-02 Trial

Under the terms of the agreement, Novartis will provide Olema with ribociclib drug supply for the planned, Olema-sponsored, Phase 3 OPERA-02 trial of palazestrant in combination with ribociclib in ER+/HER2- frontline advanced or metastatic breast cancer. All clinical data and inventions from the trial will be jointly owned while Olema maintains global commercial and marketing rights to palazestrant.

Private Placement Funds Expanded Clinical Development Activities

The Private Placement is expected to close on or about December 4, 2024, subject to the satisfaction of customary closing conditions. The financing included participation by new and existing investors Adage Capital Partners LP, Bain Capital Life Sciences, BVF Partners L.P., Driehaus Capital Management, Janus Henderson Investors, Paradigm BioCapital Advisors, Wellington Management, Woodline Partners LP, and a large investment manager. Pursuant to the terms of the securities purchase agreement, Olema will issue 19,928,875 shares of common stock at a purchase price of $9.08 per share and pre-funded warrants to purchase up to an aggregate of 7,604,163 shares of common stock at a purchase price of $9.0799 per pre-funded warrant, for gross proceeds of approximately $250.0 million, before deducting placement agent fees and other offering expenses. The pre-funded warrants will have an exercise price of $0.0001 per share of common stock, be immediately exercisable and remain exercisable until exercised in full. The Private Placement is being conducted in accordance with applicable Nasdaq rules and was priced using the average Nasdaq official closing price of Olema’s common stock for the five trading days ended November 27, 2024.

Jefferies is acting as lead placement agent with J.P. Morgan, Citigroup, Goldman Sachs & Co. LLC, LifeSci Capital, Oppenheimer & Co., and H.C. Wainwright & Co. acting as placement agents in the Private Placement.

Olema intends to use the net proceeds from the Private Placement, together with its current cash, cash equivalents and marketable securities, to fund the OPERA-02 trial, the Phase 1/2 study of OP-3136, and its ongoing Phase 3 OPERA-01 monotherapy trial of palazestrant, and for working capital and general corporate purposes.

The securities described above have not been registered under the Securities Act of 1933, as amended (the "Securities Act"), or any state’s securities laws, and are being issued and sold pursuant to an exemption from registration provided for under the Securities Act. Accordingly, these securities may not be offered or sold in the United States, except pursuant to an effective registration statement or an applicable exemption from the registration requirements of the Securities Act. Olema has agreed to file a registration statement with the U.S. Securities and Exchange Commission (the "SEC") registering the resale of the shares of common stock issued and sold in the Private Placement. Any offering of the securities under the resale registration statement will only be made by means of a prospectus.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of these securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such jurisdiction.

About Palazestrant (OP-1250)

Palazestrant (OP-1250) is a novel, orally available small molecule with dual activity as both a complete estrogen receptor (ER) antagonist (CERAN) and selective ER degrader (SERD). It is currently being investigated in patients with recurrent, locally advanced or metastatic ER-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer. In preclinical studies, palazestrant completely blocks ER-driven transcriptional activity in both ESR1 wild-type and mutant forms of breast cancer. In Olema’s ongoing clinical trials for advanced or metastatic ER+/HER2- breast cancer, palazestrant has demonstrated anti-tumor activity along with attractive pharmacokinetics and exposure, favorable tolerability, and combinability with CDK4/6 inhibitors. Palazestrant has been granted U.S. Food and Drug Administration (FDA) Fast Track designation for the treatment of ER+/HER2- metastatic breast cancer that has progressed following one or more lines of endocrine therapy with at least one line given in combination with a CDK4/6 inhibitor. It is being evaluated both as a single agent in an ongoing Phase 3 clinical trial, OPERA-01, and in Phase 1/2 combination studies with CDK4/6 inhibitors (palbociclib and ribociclib), a PI3Ka inhibitor (alpelisib), and an mTOR inhibitor (everolimus).

On December 2, 2024 Omeros Corporation (Nasdaq: OMER) reported that two abstracts directed to zaltenibart (OMS906), Omeros’ investigational inhibitor of MASP-3, the key activator of the alternative pathway of complement, will be presented at the 66th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper), to be held December 7-10, 2024 in San Diego (Press release, Omeros, DEC 2, 2024, View Source [SID1234648739]). The zaltenibart abstracts are directed to the treatment of paroxysmal nocturnal hemoglobinuria (PNH), a rare, life-threatening hematological disorder. Enrollment for the zaltenibart Phase 3 clinical trials in PNH is expected to open in early 2025.

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Both abstracts are available on the ASH (Free ASH Whitepaper) website at www.hematology.org. Details of the congress presentations and direct links to the abstracts are found below.

Monotherapy Treatment with Zaltenibart (OMS906), an Alternative Pathway Masp-3 Inhibitor, Improved Key Hematologic Parameters in Patients with PNH with a Suboptimal Response to Ravulizumab: Interim Results from a Phase 2 Proof-of-Concept Study
Abstract Number / Link: 4072
Session: 508. Bone Marrow Failure: Acquired: Poster III
Presentation Time: Monday, December 9, 2024, 6:00 PM-8:00 PM
Location: San Diego Convention Center, Halls G-H
Presenting Author: Morag Griffin, MBChB, MRCP

Population Pharmacokinetics/Pharmacodynamics and Clinical Pharmacology of Zaltenibart (OMS906) in Healthy Subjects and Patients with PNH
Abstract Number / Link: 4081
Session: 508. Bone Marrow Failure: Acquired: Poster III
Presentation Time: Monday, December 9, 2024, 6:00 PM-8:00 PM
Location: San Diego Convention Center, Halls G-H
Presenting Author: William Pullman, BMedSc, MBBS, PhD, FRACP

The presentation materials associated with each abstract will be made available on Omeros’ website at www.omeros.com following the congress presentations.

About OMS906

OMS906 is an investigational human monoclonal antibody targeting mannan-binding lectin-associated serine protease-3 (MASP-3), the key and most proximal activator of the complement system’s alternative pathway. The complement system is a critical part of innate immunity and plays a central role in host homeostasis and defense against pathogens. Responsible for the conversion of pro-complement factor D to complement factor D, MASP-3 is believed to be the premier target in the alternative pathway – it has the lowest native circulating level and low relative clearance compared to the other alternative pathway proteins and, unlike C5 and C3 blockers, MASP-3 inhibition leaves intact the lytic arm of the classical pathway, important for fighting infection. Also, unlike other components of the alternative pathway, MASP-3 is believed not to be an acute phase reactant, which could provide a significant advantage to MASP-3 inhibitors, like OMS906, over other alternative pathway inhibitors. MASP-3 inhibitors are thought to have preventive or therapeutic effects across a broad range of diseases including paroxysmal nocturnal hemoglobinuria (PNH), hemolytic uremic syndrome (HUS), atypical HUS, traumatic brain injury, arthritis, geographic atrophy or "dry" macular degeneration, ischemia-reperfusion injury, transplant-related complications and other immune-related disorders.

On December 2, 2024 Purple Biotech Ltd. ("Purple Biotech" or "the Company") (NASDAQ/TASE: PPBT), a clinical-stage company developing first-in-class therapies that overcome tumor immune evasion and drug resistance, reported positive final results from the randomized Phase 2 study of its lead oncology drug, CM24, a humanized monoclonal antibody that blocks CEACAM1, in patients with pancreatic ductal adenocarcinoma (PDAC) (Press release, Purple Biotech, DEC 2, 2024, View Source [SID1234648722]).

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"We are very excited about the final data, demonstrating CM24’s clear and consistent improvement across all efficacy endpoints evaluated in our randomized Phase 2 study," stated Purple Biotech CEO Gil Efron. "The enhanced results in patients with CEACAM1 and other serum markers gives us further optimism that a biomarker enriched patient population selection could further strengthen CM24’s magnitude of efficacy, potentially positioning CM24 as a treatment for multiple CEACAM1-expressing malignancies in line with its mechanism of action."

Michael Cecchini, MD Associate Professor of Medicine at the Yale Cancer Center, a principal investigator in this study, commented, "The promising results in PDAC, along with the identification of a potential patient subgroup that may benefit from targeting CEACAM1 and NET serum levels, potentially position CM24 as an encouraging treatment option. As a clinician, it is inspiring to see data that suggest the potential for improved outcomes in patients with late-stage metastatic PDAC, who desperately need new and effective therapies. These findings support further investigation of CM24 in combination with a checkpoint inhibitor and standard-of-care chemotherapy to improve outcomes not only in PDAC but also in other challenging cancer types."

Summary of Data and Findings:

The Phase 2 study evaluated CM24, a novel first-in-class multi-functional anti-CEACAM1 antibody, in combination with Bristol Myers Squibb’s immune checkpoint inhibitor nivolumab plus stand-of-care (SoC) chemotherapy in second-line metastatic PDAC patients versus SoC chemotherapy alone. CM24 is a humanized monoclonal antibody that blocks CEACAM1, a multi-faceted membrane glycoprotein that is one of the main proteins present on NETs, also acting as a pro-angiogenic and anti-apoptotic agent collectively promoting tumor invasiveness, metastasis and immune evasion.

The primary endpoint of the study is OS and the secondary endpoints include PFS, ORR and disease control rate (DCR). A Bayesian methodology was used to estimate the magnitude of effect of the experimental arm versus the SoC arm in each chemotherapy cohort; the study was not powered for hypothesis testing. A total of 63 patients were enrolled, across 18 centers in the U.S., Spain, and Israel in 2 parallel and independent randomized study cohorts (total of 2 arms per cohort). The experimental arms administered patients with CM24 plus nivolumab and a choice of one of two SoC chemotherapies for second-line PDAC, dependent on prior first line therapy regimen; either gemcitabine/nab-paclitaxel or liposomal irinotecan (Nal-IRI)/5-fluorouracil (5-FU) and leucovorin (LV) (Nal-IRI/5FU/LV), while the control arms administered either respective chemotherapy alone. CA19-9 as well as additional exploratory biomarkers were also evaluated. Of the 63 patients enrolled, 32 were in the gemcitabine/nab-paclitaxel study (experimental and control) and 31 were in the Nal-IRI/5FU/LV study (experimental and control). The gemcitabine/nab-paclitaxel-based part of the study was impacted by informative censoring of the control arm that led to an imbalance between the control and experimental arms, rendering this part of the study unsuitable for analysis; this part of the study has no impact on the CM24+nivolumab+Nal-IRI/5FU/LV portion of the study.

The study’s final efficacy results in the Nal-IRI/5FU/LV intent to treat (ITT) cohort population are summarized in the following table:

Metric CM24 + Nivolumab +
Nal/IRI/5FU/LV Arm
(n = 16) Nal/IRI/5FU/LV Arm
(n = 15)
Hazard ratio for OS 0.81 (95% CI: 0.38-1.71)
Median OS 7.92 months 5.55 months
6 months OS rate 53 % 47 %

Hazard Ratio for PFS 0.75 (95% CI: 0.35-1.61)
Median PFS 3.9 months 2.0 months
3 months PFS rate 67 % 47 %
6 months PFS rate 17 % 13 %
ORR 25 % 7 %
DCR 63 % 47 %

A consistent and continuous decrease of CA19-9, a clinically validated PDAC biomarker, was observed in the experimental arm reaching a median percentage reduction from baseline of approximately 80% vs. an increase of 40% in the control arm.

Subgroup analysis of patients with a range of pretreatment serum CEACAM1 between 6,000 pg/mL and 15,000 pg/mL, resulted in statistically significant results as follows:

Metric CM24 + Nivolumab +
Nal/IRI/5FU/LV Arm
(n = 4)
Nal/IRI/5FU/LV Arm
(n = 7)

Hazard ratio for OS 0.21 (95% CI: 0.04-1.06)
Median OS 9 months 3.9 months
Hazard ratio for PFS <0.1 (95% CI: 0-inf)
Median PFS 4.7 months 1.8 months
ORR 50 % 0 %
DCR 100 % 43 %

An additional subgroup analysis of patients, which comprised 80% of the patients in the study cohort, with a range of pretreatment serum CEACAM1 between 6,000 pg/mL and 15,000 pg/mL together with patients with pretreatment serum Myeloperoxidase (MPO) levels of 200 ng/mL and 600 ng/mL, resulted in statistically significant results as follows:

Metric CM24 + Nivolumab +
Nal/IRI/5FU/LV Arm
(n = 13) Nal/IRI/5FU/LV Arm
(n = 11)
Hazard ratio for OS 0.39 (95% CI: 0.16-0.98)
Median OS 7.90 months 5.50 months
Hazard ratio for PFS 0.28 (95% CI: 0.11-0.73)
Median PFS 4.1 months 1.9 months
ORR 31 % 0 %
DCR 69 % 36 %

Additional biomarkers analysis based on the patient pretreatment biopsies, demonstrated significant OS and PFS benefit (HR 0.1, P=0.013 and HR 0.19, P=0.033, respectively) in patients with both high tumor CEACAM1 (≥100) and low Combined Positive Score (CPS) (≤1) (a measure of PD-L1 positive tumor cells) supporting the CM24/nivolumab combined treatment and its mechanistic rationale, and may open a new opportunity for patients who are not eligible for anti-PD1 therapy in various indications

The CM24+nivolumab+Nal/IRI/5FU/LV regimen was well tolerated, with the most frequent treatment emergent Grade 3 or higher adverse events being diarrhea (4 patients in the experimental arm vs. 1 patient in the control arm), fatigue (2 patients in the experimental arm vs. no patients in the control) and neutropenia (2 patients in the experimental arm vs. no patients in the control). Accordingly, no meaningful difference in safety and tolerability were observed between the experimental arm and SoC arm.

"The significant results in the subgroup based on certain range of serum CEACAM1 and MPO levels, that covered 80% of the patients in the Nal-IRI cohort, is encouraging. We believe that tumors with low CEACAM1 or NETs are less reliant on these targets whereas extremely high levels may suggest potential resistance to the treatment. Based on the emerging role of neutrophil extracellular traps (NETs) in cancer and the positive findings of our study in this selected population overlapping with CEACAM1 expression, we are planning a 3-arm Phase 2b study comparing either CM24 plus a PD1 inhibitor or CM24 monotherapy to SoC in multiple tumor types selected based on their NET and CEACAM1 expressions. This design will also investigate the contribution of parts in regard to the need for PD1 blockade on top of CM24. We plan to target patients with higher serum levels of CEACAM1 and MPO, as they are potentially more likely to benefit from CM24 treatment," stated Dr Michael Schickler, Head of Clinical and Regulatory Affairs.

On December 2, 2024 Daiichi Sankyo (TSE: 4568) reported that it will present new clinical research across its oncology portfolio with more than 45 abstracts in multiple types of solid and blood cancers at the 2024 ESMO (Free ESMO Whitepaper) Asia Congress (#ESMOAsia24), San Antonio Breast Cancer Symposium (#SABCS24) and American Society of Hematology (ASH) (Free ASH Whitepaper) (#ASH24) Annual Meeting prior to its Science & Technology Day (Press release, Daiichi Sankyo, DEC 2, 2024, https://www.businesswire.com/news/home/20241127957948/en/Daiichi-Sankyo-Highlights-Progress-Across-Oncology-Portfolio-in-Multiple-Solid-and-Blood-Cancers-at-ESMO-Asia-SABCS-and-ASH [SID1234648740]).

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Data at ESMO (Free ESMO Whitepaper) Asia, SABCS and ASH (Free ASH Whitepaper) will showcase Daiichi Sankyo’s progress towards its goal of creating new standards of care for patients with cancer. Highlights include three late-breaking presentations, including a pooled analysis of data from the TROPION-Lung05 phase 2 and TROPION-Lung01 phase 3 trials of datopotamab deruxtecan (Dato-DXd) in patients with EGFR-mutated advanced non-small cell lung cancer (NSCLC) at ESMO (Free ESMO Whitepaper) Asia, as well as a subgroup analysis from the DESTINY-Breast06 phase 3 trial of ENHERTU (trastuzumab deruxtecan) in patients with unresectable or metastatic HR positive, HER2 low (IHC 1+ or IHC 2+/ISH-) or HER2 ultralow (IHC 0 with membrane staining) breast cancer and the primary analysis from the VALENTINE phase 2 trial of patritumab deruxtecan (HER3-DXd) in patients with early HR positive, HER2 negative breast cancer at SABCS.

"Important updates in difficult-to-treat cancers including lung, breast, gastric and biliary tract cancer as well as acute myeloid leukemia and peripheral T-cell lymphoma will be highlighted at these upcoming meetings," said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. "We continue to make important progress with our approved and pipeline medicines with the goal of changing the standard of care across a wide range of cancers."

Innovation in Lung, Breast, Gastric and Biliary Tract Cancer at ESMO (Free ESMO Whitepaper) Asia
Late-breaking data at ESMO (Free ESMO Whitepaper) Asia will highlight a pooled analysis of results from the TROPION-Lung05 phase 2 and TROPION-Lung01 phase 3 trials of datopotamab deruxtecan in patients with previously treated EGFR-mutated advanced NSCLC during a proffered paper session.

Two mini oral presentations will feature results of the TROPION-Breast01 phase 3 trial of datopotamab deruxtecan in Chinese patients with previously treated metastatic HR positive, HER2 low or negative breast cancer and the final results of the DESTINY-Gastric06 phase 2 trial of ENHERTU in Chinese patients with previously treated HER2 positive advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma. Results of DESTINY-Gastric06 led to the recent conditional approval in China of ENHERTU as a monotherapy for the treatment of adult patients with locally advanced or metastatic HER2 positive gastric or GEJ adenocarcinoma who have received two or more prior treatment regimens.

Trials-in-progress posters also will feature the trial designs of three ongoing ENHERTU clinical trials, including the DESTINY-BTC01 phase 3 trial that will evaluate ENHERTU with rilvegostomig, AstraZeneca’s PD-1/TIGIT bispecific antibody, versus standard of care in patients with previously untreated HER2 expressing, locally advanced or metastatic biliary tract cancer, and the DESTINY-Gastric03 phase 1b/2 trial where a new arm has been added to evaluate ENHERTU in combination with rilvegostomig and chemotherapy in patients with HER2 positive or HER2 low gastric or GEJ adenocarcinoma. A second part of the DESTINY-PanTumor02 phase 2 trial of ENHERTU also will be presented where patients with previously treated HER2 expressing metastatic solid tumors will be enrolled into one of five new cohorts: patients with any tumor expressing HER2 IHC 3+ (excluding breast, gastric and colorectal cancer); patients with any tumor expressing HER2 IHC 2+/ISH+ (excluding breast, gastric and colorectal cancer); patients with HER2 IHC 2+/1+ endometrial cancer; patients with HER2 IHC 2+/1+ ovarian cancer; and patients with HER2 IHC 2+/1+ cervical cancer.

Continued Progress in Breast Cancer at SABCS
Late-breaking presentations in breast cancer at SABCS will include two oral presentations featuring a subgroup analysis of the DESTINY-Breast06 phase 3 trial reporting on the impact of response to prior endocrine-based therapy on outcomes in patients with unresectable or metastatic HR positive, HER2 low or HER2 ultralow breast cancer who failed at least one line of endocrine therapy receiving ENHERTU compared to chemotherapy, and the primary results from the VALENTINE phase 2 trial evaluating neoadjuvant patritumab deruxtecan (HER3-DXd) alone or in combination with letrozole in patients with high-risk HR positive, HER2 negative early breast cancer.

Other data at SABCS includes two spotlight poster presentations highlighting the first exploratory biomarker analysis assessing the impact of genomic alterations on the efficacy of ENHERTU compared to ado-trastuzumab emtansine (T-DM1) in patients with HER2 positive metastatic breast cancer from the DESTINY-Breast03 phase 3 trial, and the effects of ENHERTU on health-related quality of life and neurological function from the DESTINY-Breast12 phase 3b/4 trial in patients with previously treated HER2 positive metastatic breast cancer with or without brain metastases. Final results from the dose expansion portion of the DESTINY-Breast08 phase 1b trial evaluating ENHERTU in combination with capecitabine or capivasertib in patients with HER2 low metastatic breast cancer also will be presented as a poster presentation.

Trial-in-progress posters will feature the trial designs from a sub-protocol of a phase 1b master protocol trial evaluating ENHERTU in combination with valemetostat, a dual EZH1 and EZH2 inhibitor, in patients with previously treated HER2 low unresectable or metastatic breast cancer as well as a phase 1b trial evaluating the combination in patients with previously treated HER2 low, HER2 ultralow or HER2 null metastatic breast cancer.

Updates in Hematology Portfolio in Certain Leukemias and Lymphomas
At ASH (Free ASH Whitepaper), several sub-analyses of the QuANTUM-First phase 3 trial of VANFLYTA (quizartinib) in patients with newly diagnosed FLT3-ITD positive acute myeloid leukemia (AML) will be presented. An oral presentation will highlight data on the frequency of co-mutations in trial patients and their impact on remission rate, overall survival and relapse-free survival. Three poster presentations will report new data, including the impact of continuation therapy on the efficacy of VANFLYTA, focusing on measurable residual disease status; a concordance between utilizing a FLT3-ITD mutation detection clinical trial assay and a next-generation sequencing measurable residual disease assay; and a matching adjusted indirect comparison analysis of VANFLYTA compared to midostaurin in patients with newly diagnosed FLT3-ITD AML.

Additionally, several poster presentations will report on the QUIWI phase 2 trial that evaluated VANFLYTA in combination with standard chemotherapy in patients with newly diagnosed FLT3-ITD negative AML, including the final results of QUIWI and sub-analyses of the trial by mutational status, including FLT3-TKD and NPM1, and ELN risk categorization. The QUIWI phase 2 trial formed the basis of the QuANTUM-Wild phase 3 trial that is further evaluating the addition of VANFLYTA to standard chemotherapy in this patient population. The design of the QuANTUM-Wild phase 3 trial will be highlighted as a trial-in-progress poster.

Other data at ASH (Free ASH Whitepaper) includes two poster presentations reporting the primary results of the VALYM phase 2 trial of valemetostat in patients with relapsed or refractory large B-cell lymphoma and an exploratory analysis of circulating tumor DNA, a novel biomarker, to potentially predict clinical response to valemetostat from the VALENTINE-PTCL01 phase 2 trial in patients with relapsed or refractory peripheral T-cell lymphoma, which was recently published in The Lancet Oncology.

Science & Technology Day
Daiichi Sankyo will hold "Science & Technology Day," formerly called R&D Day, for investors on Monday, December 16, 2024 from 5:30 to 7:30 pm EST / Tuesday, December 17 from 7:30 to 9:30 am JST. Executives from Daiichi Sankyo will provide an overview of the ESMO (Free ESMO Whitepaper) Asia, SABCS and ASH (Free ASH Whitepaper) research data and provide updates on R&D strategy.

ESMO Asia, SABCS and ASH (Free ASH Whitepaper) Data Highlights
Highlights of data from Daiichi Sankyo’s DXd ADC portfolio at ESMO (Free ESMO Whitepaper) Asia 2024 include:

Presentation Title

Author

Abstract

Presentation (SGT)

Datopotamab Deruxtecan (Dato-DXd)

Lung Cancer

Efficacy and safety of datopotamab deruxtecan (Dato-DXd) in patients with previously treated EGFR-mutated advanced non-small cell lung cancer: a pooled analysis of TROPION-Lung01 and TROPION-Lung05

M. Ahn

LBA7

Proffered Paper Session

Friday, December 6

10:15 – 11:45 am

Breast Cancer

Datopotamab deruxtecan (Dato-DXd) vs chemotherapy in patients with pre-treated inoperable/metastatic hormone receptor positive, HER2 negative breast cancer: results from TROPION-Breast01 China cohort

S. Wang

38MO

Mini Oral Session

Saturday, December 7

2:30 – 3:40 pm

ENHERTU (trastuzumab deruxtecan; T-DXd)

Gastric

Cancer

Trastuzumab deruxtecan (T-DXd) in Chinese patients with previously treated HER2 positive advanced gastric or gastroesophageal junction adenocarcinoma: DESTINY-Gastric06 final analysis

Z. Peng

129MO

Mini Oral Session

Saturday, December 7

9:00 – 10:40 am

A phase 1b/2 open-label study evaluating trastuzumab deruxtecan (T-DXd) in combination with rilvegostomig and chemotherapy in patients with HER2 positive and HER2 low gastric or gastroesophageal junction adenocarcinoma: DESTINY-Gastric03 part 4

Y. Janjigian

264TiP

Poster Session

December 7, 2024

5:50 – 6:45 pm

PanTumor

Randomized, open-label, multicenter, phase 3 study of trastuzumab deruxtecan (T-DXd) with rilvegostomig vs standard of care in first-line HER2 expressing, locally advanced or metastatic biliary tract cancer: DESTINY-BTC01

M. Ikeda

261TiP

Poster Session

December 7, 2024

5:50 – 6:45 pm

An open-label, multicenter, phase 2 study of trastuzumab deruxtecan (T-DXd) in patients with HER2 expressing solid tumors: DESTINY-PanTumor02 part 2

J. Lee

400TiP

Poster Session

December 7, 2024

5:50 – 6:45 pm

Highlights of data from Daiichi Sankyo’s DXd ADC portfolio at SABCS 2024 include:

Presentation Title

Author

Abstract

Presentation (CST)

ENHERTU (trastuzumab deruxtecan; T-DXd)

HER2 Low & HER2 Ultralow Breast Cancer

Efficacy and safety of trastuzumab deruxtecan (T-DXd) vs physician’s choice of chemotherapy by pace of disease progression on prior endocrine-based therapy: an additional analysis from DESTINY-Breast06

A Bardia

LB1-04

Oral Session

Tuesday, December 10

6:00 – 7:00 pm

Trastuzumab deruxtecan in combination with capecitabine or capivasertib in patients with HER2 low metastatic breast cancer: a phase 1b, multicenter, open-label study (DESTINY-Breast08)

K. Jhaveri

P3-09-17

Poster Session

Thursday, December 12

12:30 – 2:00 pm

A real-world study of the effectiveness and safety of trastuzumab deruxtecan in HER2 low metastatic breast cancer among racial and ethnic minorities and older populations in the United States

M. Henderson

P2-12-20

Poster Session

Wednesday, December 11

5:30 – 7:00 pm

Agreement between the DESTINY-Breast04/06 VENTANA 4B5 HER2 IHC clinical trial assay and other comparator assays for HER2 low breast cancer: overall results of a large-scale, multicenter global ring study

G. Viale

P1-03-28

Poster Session

Wednesday, December 11

12:30 – 2:00 pm

Trastuzumab deruxtecan in HER2 low metastatic breast cancer patients with newly diagnosed or progressing brain metastases: the TUXEDO-4 phase II trial

M. Marhold

P3-08-21

Poster Session

Thursday, December 12

12:30 – 2:00 pm

Re-evaluation of human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) 0 or 1+ in metastatic breast cancer samples to characterize the proportion of HER2 ultralow (IHC 0 with membrane staining)

S. Krishnamurthy

P3-09-20

Poster Session

Thursday, December 12

12:30 – 2:00 pm

Valemetostat and trastuzumab deruxtecan in patients with HER2 low, previously treated, unresectable or metastatic breast cancer

S. Tolaney

P3-08-24

Poster Session

Thursday, December 12

12:30 – 2:00 pm

Phase 1b study of EZH1/2 inhibitor valemetostat in combination with trastuzumab deruxtecan in subjects with HER2 low/ultra-low/null metastatic breast cancer

T. Iwase

P3-12-28

Poster Session

Thursday, December 12

12:30 – 02:00 pm

HER2 Positive Breast Cancer

Exploratory biomarker analysis of trastuzumab deruxtecan vs trastuzumab emtansine efficacy in human epidermal growth factor receptor 2-positive metastatic breast cancer in DESTINY-Breast03

W. Jacot

PS8-03

Spotlight Poster Session

Thursday, December 12

7:00 – 8:30 am

Effects of trastuzumab deruxtecan (T-DXd) on health-related quality of life and neurological function in patients with HER2+ advanced/metastatic breast cancer with or without brain metastases: DESTINY-Breast12 results

N. Harbeck

PS14-10

Spotlight Poster Session

Friday, December 13

7:00 – 8:30 am

Real-world analysis of interstitial lung disease in patients with HER2-positive unresectable or recurrent breast cancer treated with trastuzumab deruxtecan: all-patient post-marketing surveillance study in Japan

J. Tsurutani

P1-02-10

Poster Session

Wednesday, December 11

12:30 – 2:00 pm

HER2 Expressing Breast Cancer

Trastuzumab deruxtecan with pembrolizumab in previously treated HER2 expressing advanced or metastatic breast cancer: interim analyses of the breast cohorts from the open-label, multicenter, phase 1b study DS8201-A-U106

H. Rugo

P5-07-29

Poster Session

Friday, December 13

12:30 – 2:00 pm

Patritumab Deruxtecan (HER3-DXd)

HR Positive, HER2 Negative Breast Cancer

Primary results of SOLTI VALENTINE: neoadjuvant randomized phase II trial of HER3-DXd alone or in combination with letrozole for high-risk hormone receptor positive/HER2-negative early breast cancer

M. Oliveira

LBA1-06

Oral Presentation

Tuesday, December 10

6:00 – 7:00 pm

ICARUS-BREAST02: safety, tolerability, and anti-tumor activity of patritumab deruxtecan (HER3-DXd) monotherapy and combinations in patients with inoperable advanced breast cancer following progression on trastuzumab deruxtecan (T-DXd)

B. Pistilli

P2-08-27

Poster Presentation

Wednesday, December 11

5:30 – 7:00 pm

Highlights of data from Daiichi Sankyo’s hematology portfolio at ASH (Free ASH Whitepaper) 2024 include:

Presentation Title

Author

Abstract

Presentation (PST)

VANFLYTA (quizartinib)

FTL3 -ITD Positive AML

Correlation of baseline gene mutations with quizartinib efficacy in patients with FLT3-ITD positive newly diagnosed acute myeloid leukemia in the phase 3 QuANTUM-First trial

M. Levis

848

Oral Presentation

Monday, December 9

3:00 – 3:15 pm

QuANTUM-First: effects of quizartinib on RFS, OS, CIR, and MRD in newly diagnosed patients with FMS-like tyrosine kinase 3-internal tandem duplication positive (FLT3-ITD+) acute myeloid leukemia who received continuation therapy

M. Levis

2890

Poster Presentation

Sunday, December 8

6:00 – 8:00 pm

QuANTUM-First: deep-dive analysis of FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) detection methods utilized for enrollment and longitudinal MRD detection in newly diagnosed patients with FLT3-ITD+ acute myeloid leukemia

J. Rohrbach

4278

Poster Session

Monday, December 9

6:00 – 8:00 pm

Anchored matching adjusted indirect treatment comparison of quizartinib vs midostaurin in newly diagnosed patients with FLT3-ITD positive acute myeloid leukemia

S. Unni

1509

Poster Session

Saturday, December 7

5:30 – 7:30 pm

FLT3-ITD Negative AML

Trial in progress: the phase 3, randomized, double-blind, placebo-controlled QuANTUM-Wild study of quizartinib in combination with chemotherapy and as single-agent maintenance in newly diagnosed FLT3-ITD negative acute myeloid leukemia

P. Montesinos

1504.3

Poster Session

Saturday, December 7

5:30 – 7:30 pm

Final results of QUIWI: a double blinded, randomized PETHEMA trial comparing standard chemotherapy plus quizartinib versus placebo in adult patients with newly diagnosed FLT3-ITD negative AML

P. Montesinos

1512

Poster Session

Saturday, December 7

5:30 – 7:30 pm

Enhanced validation of the FLT3-like gene expression signature as a predictive biomarker for quizartinib response in FLT3-ITD negative acute myeloid leukemia: expanded cohort and extended follow-up from the PETHEMA QUIWI trial

A.

Mosquera

Orgueira

1552

Poster Session

Saturday, December 7

5:30 – 7:30 pm

Correlation of ELN-risk and gene mutations with quizartinib efficacy in patients with FLT3-ITD negative newly diagnosed acute myeloid leukemia in the phase 2 QUIWI PETHEMA trial

R. Rodriguez- Viega

2895

Poster Session

Sunday, December 8

6:00 – 8:00 pm

Valemetostat (EZHARMIA in Japan only)

B-Cell & T-Cell

Lymphomas

Valemetostat monotherapy in patients with relapsed or refractory large B-cell lymphoma: primary results of the phase 2 VALYM study from the LYSA

E. Bachy

4479

Poster Session

Monday, December 9

6:00 – 8:00 pm

Prediction of clinical response by phased variants in circulating tumor DNA (ctDNA) in the VALENTINE-PTCL01 trial of patients with relapsed or refractory peripheral T-cell lymphoma

N. Mehta-Shah

4342

Poster Session

Monday, December 9

6:00 – 8:00 pm

About the ADC Portfolio of Daiichi Sankyo
The Daiichi Sankyo ADC portfolio consists of seven ADCs in clinical development crafted from two distinct ADC technology platforms discovered in-house by Daiichi Sankyo.

The ADC platform furthest in clinical development is Daiichi Sankyo’s DXd ADC Technology where each ADC consists of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. The DXd ADC portfolio currently consists of ENHERTU, a HER2 directed ADC, and datopotamab deruxtecan (Dato-DXd), a TROP2 directed ADC, which are being jointly developed and commercialized globally with AstraZeneca. Patritumab deruxtecan (HER3-DXd), a HER3 directed ADC, ifinatamab deruxtecan (I-DXd), a B7-H3 directed ADC, and raludotatug deruxtecan (R-DXd), a CDH6 directed ADC, are being jointly developed and commercialized globally with Merck & Co., Inc, Rahway, NJ, USA. DS-3939, a TA-MUC1 directed ADC, is being developed by Daiichi Sankyo.

The second Daiichi Sankyo ADC platform consists of a monoclonal antibody attached to a modified pyrrolobenzodiazepine (PBD) payload. DS-9606, a CLDN6 directed PBD ADC, is the first of several planned ADCs in clinical development utilizing this platform.

Datopotamab deruxtecan, ifinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan, DS-3939 and DS-9606 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established.