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Pictured: Exterior view of Pfizer's office in Belgium/iStock, Alexandros Michailidis Pfizer on Tuesday released results for the Phase III ECHELON-3 study, demonstrating that the antibody-drug conjugate Adcetris (brentuximab vedotin) significantly boosted survival in patients with relapsed/refractory diffuse large B-cell lymphoma when used with lenalidomide and rituximab. The pharma did not provide specific data in its announcement, disclosing only that the Adcetris-based regimen led to a “statistically significant and clinically meaningful” improvement in overall survival versus lenalidomide and rituximab plus placebo. The Adcetris combo also led to “positive outcomes” in various key secondary endpoints, including overall response rate and progression-free survival. In terms of safety, Adcetris’ tolerability and adverse event pro consistent with what had previously been established for the antibody-drug conjugate (ADC) in relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Roger Dansey, chief development officer of oncology at Pfizer, in a statement said that these data from ECHELON-3 indicate that Adcetris “could address an area of high unmet need in patients with relapsed or refractory DLBCL irrespective of CD30 expression.” “These results are particularly encouraging because the study evaluated heavily pre-treated patients, including some who received prior CAR-T therapy,” Dansey added. Originally developed by Seagen in collaboration with Takeda, Adcetris is an ADC that targets the CD30 surface protein, which is commonly expressed by certain blood cancers but not healthy cells. According to Seagen’s website, Adcetris carries a toxic payload called monomethyl auristatin E, which it releases inside the malignant cells triggering cell death. Pfizer secured access to Adcetris in March 2023, when it bought Seagen for $43 billion. Adcetris was first approved in August 2011 for the treatment of Hodgkin lymphoma and the rare systemic anaplastic large cell lymphoma. The ADC has since picked up several other approvals, allowing its use in other treatment settings and patient populations for these cancers. The pharma partners are continuing to develop Adcetris in other subtypes and stages of Hodgkin lymphoma, peripheral T-cell lymphoma, non-small cell lung cancer and melanoma. Tuesday’s readout will help Pfizer further deepen its expertise in ADC technology and expand its footprint in the space. Earlier this month, the pharma laid out its plans for its oncology franchise in the coming years. Key to its new strategy is a refined focus on four cancer types, which include hematologic malignancies such as lymphomas and multiple myeloma. Pfizer is also looking to build up its biologics business, which it expects to comprise approximately 65% of its cancer franchise by 2030, up from its current 6% mix. The Seagen acquisition, with its deep ADC portfolio, will contribute heavily to potentially meeting this target. Beyond Seagen, Pfizer in December 2023 also inked a potential $1.05 billion contract with Nona Biosciences to develop the Massachusetts-based biotech’s early-stage mesothelin-targeting ADC HBM9033 in solid tumors. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

Clinical-stage CAR-T company is actively recruiting patients to evaluate SynKIR™-110, a new treatment candidate for ovarian cancer, mesothelioma, and cholangiocarcinoma PHILADELPHIA, March 7, 2024 /PRNewswire/ -- Verismo Therapeutics, a clinical-stage CAR-T company developing the novel KIR-CAR platform technology, today announced that it has activated a second clinical site for its STAR-101 Phase 1 clinical trial at The University of Texas MD Anderson Cancer Center. STAR-101 is a multi-center clinical trial designed to evaluate Verismo Therapeutic's lead candidate, SynKIR™-110, for the treatment of mesothelin-overexpressing ovarian cancer, malignant pleural mesothelioma, and cholangiocarcinoma. "This milestone marks the steady progress towards our goal of bringing SynKIR™-110 to as many patients as possible," said Dr. Bryan Kim, Co-Founder and CEO of Verismo Therapeutics. "We are grateful for the opportunity to work with Dr. Mehmet Altan at MD Anderson to bring us closer to that goal." Verismo achieved clearance from the FDA to initiate this multi-center clinical trial for SynKIR™-110 and has partnered with the Hospital of the University of Pennsylvania as the first clinical site. Verismo has previously announced that SynKIR™-110 received Orphan Drug Designation and Fast Track Designation for the treatment of mesothelin-expressing mesotheliomas. For more information about the STAR-101 clinical trial, please visit ClinicalTrials.gov NCT05568680. About the KIR-CAR Platform The KIR-CAR platform is a dual-chain CAR T cell therapy and has been shown in preclinical animal models to be capable of maintaining antitumor T cell activity even in challenging solid tumor environments. DAP12 acts as a novel costimulatory molecule for T cells using additional T cell stimulating pathways, further sustaining chimeric receptor expression and improving KIR-CAR T cell functional persistence. This continued T cell function and persistence can lead to ongoing regression of solid tumors in preclinical models, including those resistant to traditional CAR T cell therapies. The KIR-CAR platform is being investigated in combination with many additional emerging technologies, such as in vivo gene engineering, advanced cell manufacturing and reprogramming, combinational therapies, and even allogeneic cellular therapies to potentially provide the next-generation multimodal targeted immunotherapy for patients in need. About Verismo Therapeutics Verismo Therapeutics is a pioneer in dual-chain KIR-CAR technology, with its first asset SynKIR™-110 under investigation in a first-in-human clinical trial. Verismo is the only company developing the KIR-CAR platform, a modified NK-like receptor designed to improve persistence and efficacy against aggressive solid tumors. The KIR-CAR platform technology was developed specifically for advanced solid tumors, an area of high unmet medical need. For more information, visit: CONTACT: Raymond Luke, raymond.luke@verismotherapeutics.com

Takeda’s pipeline cull affected assets outside of oncology. Takeda’s vision of becoming a leader in oncology ran into more trouble Thursday when the drugmaker axed (PDF) a midphase immunocytokine and three early-stage CAR-T cell therapy prospects from its R&D pipeline. Under CEO Christophe Weber, Takeda has worked to establish itself as a leader in oncology. But, as the executive said on a quarterly results call with investors, the company has “had some wins ... [and] some setbacks.” The results brought news of more setbacks, with Takeda using the update to reveal it has dropped a clutch of cancer candidates led by modakafusp alfa. Formerly known as TAK-573, modakafusp alfa consists of two interferon alpha-2b molecules fused to an anti-CD38 monoclonal antibody. The idea was to activate innate and adaptive immune cells—while also directly stopping the proliferation of multiple myeloma cells—through targeted interferon signaling. Takeda began a phase 1/2a Darzalex combination trial one year ago, adding to the slate of studies run in support of the immunocytokine, but has now pulled the plug on the program. Andrew Plump, M.D., Ph.D., president of R&D at Takeda, explained the decision on the conference call with investors.  “This is a strategic decision based on a number of factors, including the existing data set, the rapidly evolving multiple myeloma treatment landscape and the long development timelines,” the R&D chief said.  Takeda pushed modakafusp alfa out of the door as part of a pipeline clear-out that also hit three phase 1 autologous CAR-T candidates. Two of the prospects, GPC3-targeted TAK-102 and mesothelin-directed TAK-103, were in development in solid tumors. The third asset, TAK-940, was a CD19-directed, Memorial Sloan Kettering Cancer Center-partnered program that used the 1XX domain to try to enhance efficacy. While Takeda axed a clutch of cancer candidates, Plump said the company “remains committed to oncology and will continue to develop therapies across hematologic and solid tumors.” The R&D chief highlighted the SUMO inhibitor subasumstat, a pair of STING agonists and two T-cell engagers from the Maverick Therapeutics acquisition as candidates to watch.  Plump also cited the appointment of PK Morrow, who joined Takeda from CRISPR Therapeutics last month, as a boost for the oncology unit. Morrow became head of the oncology therapeutic area unit at Takeda, having previously worked as chief medical officer of CRISPR, and held various roles at Amgen. Takeda’s pipeline cull also affected assets outside of oncology. The drugmaker removed three phase 2 drug candidates, namely the rare disease asset TAK-611—which flunked a trial last year—the Parkinson’s disease prospect TAK-071 and the depression molecule TAK-041. In phase 1, Takeda axed treatments for Alzheimer’s disease and nausea as well as a Zika vaccine candidate. Amid the changes, Takeda grew its R&D spend by 7.3%, although Chief Financial Officer Costa Saroukos said that “does reflect some phasing,” and the company is still aiming for a mid single digit increase over the full year. Saroukos made the comment on what looks set to be his last quarterly results conference call as CFO of Takeda.  Milano Furuta, president of Takeda’s Japan pharma business unit, is preparing to take over as CFO in April. Saroukos is leaving because “after 20 years working abroad, I’m ready to move back to Australia to be closer to my family,” the outgoing CFO told investors.