Boehringer Ingelheim Announces Promising Findings From Groundbreaking Study on Diabetic Macular Ischemia 

Boehringer Ingelheim released encouraging results from the HORNBILL Phase I/IIa trial of BI 764524, marking the pioneering investigation into a potential therapy for individuals with diabetic macular ischemia (DMI). The research revealed that BI 764524 was well received when administered intravitreally in both single and multiple doses, successfully achieving its main safety objectives while demonstrating initial indications of effectiveness.

Diabetic macular ischemia is a frequent and permanent consequence of diabetic retinopathy with the potential to cause vision loss. It occurs when the central retina’s light-sensitive tissues experience prolonged insufficient blood flow. Presently, there are no authorized treatments for DMI.

The prevailing method of treating advanced diabetic retinopathy typically involves administering anti-VEGF injections into the eye or resorting to laser procedures. Despite these efforts, some patients experience continued deterioration. BI 764524 presents a fresh approach by targeting the Sema3A pathway to encourage re-vascularization in ischemic regions, offering potential advantages over conventional anti-VEGF and laser therapies.

Dr. Quan Dong Nguyen, a distinguished Ophthalmology Professor at Stanford School of Medicine and lead investigator of the HORNBILL study, expressed optimism regarding the findings. According to him, the study indicates a promising avenue for early intervention that could potentially reduce the risk of, and perhaps even prevent, individuals with diabetic retinopathy from experiencing irreversible and sight-threatening complications like DMI. Dr. Nguyen highlighted that retinal non-perfusion, a significant contributor to vision loss in diabetic retinopathy patients, had not been previously investigated as a potential target for treatment until the HORNBILL study.

HORNBILL is among the 23 abstracts showcased at the 2024 Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO). These abstracts cover various aspects of Boehringer Ingelheim’s retinal health portfolio, such as studies on retinal non-perfusion and diabetic retinopathy, geographic atrophy, and neovascular age-related macular degeneration.

Novartis Expands Radioligand Therapy Portfolio With Acquisition of Mariana Oncology

Novartis has announced its intention to purchase Mariana Oncology, a biotech company in Watertown, Massachusetts. Mariana Oncology specializes in developing new radioligand therapies (RLTs) for treating cancers with significant unmet medical needs. This acquisition strengthens Novartis’ RLT pipeline and enhances its capabilities in research and clinical supplies, aligning with the company’s strategic focus on oncology and RLT platform advancement. The deal includes a diverse portfolio of RLT programs covering various solid tumor types like breast, prostate, and lung cancer. One of the key candidates in development is MC-339, an RLT utilizing actinium, currently under investigation for treating small-cell lung cancer.

“The purchase of Mariana Oncology demonstrates our dedication to radioligand therapy as a pivotal technology for our company, enhancing our prominence in this area,” stated Fiona Marshall, Novartis’ President of Biomedical Research. “We’re enthusiastic about collaborating with Mariana’s team to advance next-generation RLTs for cancer patients and collectively influence the trajectory of RLT as a cornerstone in oncology treatment.”

RLTs, also known as radiopharmaceuticals, represent a specialized form of precision medicine. They merge a tumor-seeking molecule (ligand) with a therapeutic radioisotope (a radioactive element). RLTs attach to particular receptors present on the surface of specific tumor types. Upon binding to a target cell, emissions from the therapeutic radioisotope induce DNA harm, which can impede cell proliferation and, potentially, prompt cell demise. This focused strategy facilitates the administration of radiation to the tumor while minimizing harm to neighboring cells.

Currently, Novartis boasts approval for two Radio-Ligand Therapies (RLTs) catering to specific groups suffering from metastatic castration-resistant prostate cancer and select types of gastroenteropancreatic neuroendocrine tumors. Additionally, Novartis’s pipeline, encompassing both early and late-stage developments, features numerous programs either in clinical phases or poised to enter them. These initiatives span a range of studies and assets targeting prostate cancer, alongside various preclinical and discovery endeavors geared toward uncovering fresh RLT innovations. Novartis remains actively engaged in the exploration of new isotopes and combinations with complementary modes of action, while also venturing into new disease territories suitable for RLT applications. As part of the agreement, Novartis commits to an initial payment of USD 1 billion, with an additional USD 750 million earmarked for milestone achievements.

Astellas Partners with Poseida Therapeutics to Pioneer Novel Allogeneic Cell Therapies in Cancer Research

Astellas Pharma Inc. and Poseida Therapeutics, Inc. have revealed a partnership where Xyphos Biosciences, Inc. and Poseida will collaborate and license their respective cell therapy technologies to create new convertibleCAR® programs.

Poseida is making strides in specialized cell and gene treatments that have the potential to effectively treat specific cancers and uncommon illnesses. Within the field of cancer treatment, Poseida is developing advanced allogeneic CAR-T cell therapy options for both solid and liquid tumors, focusing on patient groups facing significant medical needs. Xyphos, on the other hand, employs a unique ACCELTM technology platform, leveraging its convertibleCAR® alongside proprietary MicAbodies to target tumor cells.

According to the terms outlined in the agreement, the companies intend to merge Poseida’s exclusive allogeneic CAR-T platform with Xyphos’ ACCELTM technology to craft a singular CAR-T construct developed by Poseida. This construct will serve as the foundation for two convertibleCAR® product candidates aimed at treating solid tumors. Poseida will be reimbursed by Xyphos for expenses associated with the research agreement and will oversee the development phase, with Xyphos taking charge of future commercialization efforts for products resulting from the collaboration. Poseida will receive an initial payment of US $50 million, along with potential milestone payments tied to development progress and sales, totaling up to US $550 million. Furthermore, Poseida stands to earn royalties in the low double digits as a percentage of net sales.

“We’re thrilled to strengthen our collaboration with Astellas, as we both believe in the potential of advanced, readily available cell therapies to tackle pressing challenges faced by patients with solid tumor cancers. This new agreement underscores the financial worth of Poseida’s innovative non-viral technologies and allows us to explore development opportunities beyond our primary areas of focus. It also emphasizes Poseida’s position as the preferred partner for allogeneic CAR-T therapies.”

Kristin Yarema, Ph.D., President and CEO of Poseida

In August 2023, Astellas and Poseida revealed significant financial backing from Astellas aimed at bolstering Poseida’s dedication to revolutionizing cancer cell therapy.

Prime Medicine Secures FDA Clearance for IND Application of PM359 in Treating Chronic Granulomatous Disease

Prime Medicine, Inc. declared that the FDA has approved the company’s Investigational New Drug (IND) application for PM359, submitted on March 29, for addressing chronic granulomatous disease (CGD). This clearance allows the company to commence its worldwide Phase I/II clinical trial in the United States.

“We’re excited to reach this important milestone with our inaugural product candidate, PM359. This marks the first-ever clearance for an IND for a Prime Editor product candidate, signifying a significant leap forward in next-generation gene editing,” stated Keith Gottesdiener, M.D., President and CEO of Prime Medicine. “Based on our preclinical data, we’re optimistic about PM359’s ability to effectively address a prevalent disease-causing mutation of CGD, potentially improving the condition for affected patients. We eagerly anticipate commencing our Phase I/II trial and further exploring PM359’s therapeutic potential in treating this debilitating disease.”

The Phase I/II clinical trial, conducted across multiple countries, marks the first human testing of PM359. Its primary objectives are to evaluate the safety, biological effects, and initial effectiveness of PM359 in both adults and children involved in the study. Initially, the trial will focus on adults with stable disease. Should this group demonstrate safety and biological activity, the trial will expand to include individuals with active infections or severe inflammation, as well as adolescents and children. Throughout the trial, participants will be closely monitored for safety, including the recovery and functioning of the hematopoietic system, early indicators of restored immune function, and the long-term management of infectious and inflammatory complications associated with CGD. Prime Medicine anticipates releasing preliminary clinical findings from the trial in 2025.

TIVDAK Receives Full FDA Approval for Treating Recurrent or Metastatic Cervical Cancer

Pfizer Inc. and Genmab A/S have revealed that the FDA has given its approval to the supplemental Biologics License Application (sBLA) for TIVDAK® (tisotumab vedotin-tftv), granting full authorization for its use in treating patients facing recurrent or metastatic cervical cancer whose condition has advanced despite prior chemotherapy.

Dr. Chris Boshoff, Pfizer’s Chief Oncology Officer, emphasized the urgent need for effective treatments for recurrent or metastatic cervical cancer, a condition that typically lacks viable cure options. He highlighted the significance of the FDA’s full approval for TIVDAK, underscoring its role as the initial antibody-drug conjugate demonstrating statistically significant improvements in overall survival.

Approval for TIVDAK stems from the outcomes of the global, randomized, Phase III innovaTV 301 clinical trial (NCT04697628). This trial successfully achieved its primary objective, illustrating a survival benefit in adult patients with recurrent or metastatic cervical cancer who had been previously treated with TIVDAK compared to chemotherapy. Additionally, the trial met secondary objectives related to progression-free survival (PFS) and confirmed objective response rate (ORR). The findings from the innovaTV 301 study were showcased during the Presidential session at the European Society of Medical Oncology (ESMO) Congress in October 2023.

The research findings from the innovaTV 301 trial revealed a significant 30% decrease in the likelihood of death when compared to chemotherapy. Patients treated with TIVDAK experienced a median Overall Survival (OS) of 11.5 months, whereas those on chemotherapy had a median OS of 9.5 months.

The FDA granted a Priority Review Designation to the sBLA application, indicating potential significant advancements in treatment or filling a gap where adequate therapy is lacking. TIVDAK initially received accelerated approval in the U.S. in September 2021 based on promising results from the innovaTV 204 pivotal Phase II single-arm clinical trial, which assessed its efficacy in patients with recurrent or metastatic cervical cancer. With the FDA’s approval of the sBLA, TIVDAK’s status shifts from accelerated approval to full approval in the U.S.