On May 22, 2025 FORE Biotherapeutics, a registration stage biotherapeutics company dedicated to developing targeted therapies to treat patients with cancer, reported a $38 million Series D-2 financing (Press release, Fore Biotherapeutics, MAY 22, 2025, View Source [SID1234653303]). For this initial close of the Series D-2, leading healthcare dedicated investors participated, including SR One, Medicxi, OrbiMed, HBM Healthcare Investments, Wellington Management, Novartis Venture Fund, Cormorant Asset Management, and 3B Future Health Fund. This $38 million adds to the $75 million raised as part of the earlier Series D and D-1 financings, for an aggregate total to date of $113 million for this Series D financing.

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"At SR One, our mission is to invest in companies that we believe have the ability to innovate and advance transformational new therapies in areas of high unmet medical need," said Simeon George, M.D., Chief Executive Officer and Managing Partner at SR One. "Fore Bio is focused on resetting the standard in BRAF driven tumors with a potential first in class paradox breaker with compelling early clinical data that support the potential of plixorafenib monotherapy to address the well-known treatment gaps oncologists face with first- and second-generation BRAF inhibitors. We are impressed with the team’s progress to date, excited about the multiple near term data readouts, and are proud to support the continued advancement of plixorafenib."

"This financing is a testament to the hard work of our team in developing plixorafenib, a differentiated, rationally designed BRAF inhibitor for both V600 and non V600 mutations that has already generated compelling data to date. We believe plixorafenib has the potential to overcome the limitations of currently available BRAF inhibitors, representing a multi-billion-dollar market opportunity," said William Hinshaw, Chief Executive Officer of Fore. "We are grateful for the continued support of this highly regarded investor syndicate and their confidence in both the Fore Bio team and plixorafenib. With their backing, we are well positioned to continue our capitally efficient execution and make significant strides in delivering the ongoing FORTE Master Protocol as we look to multiple anticipated interim analyses and clinical data supporting potential registration under the accelerated approval pathway with FDA submissions potentially at the end of next year."

Proceeds from the financing will be used to advance the registration-intended FORTE Master Protocol, a global Phase 2 clinical trial which includes four sub-protocol baskets evaluating plixorafenib in distinct patient populations. The three monotherapy indications currently under evaluation are BRAF V600 Recurrent Primary Central Nervous System (CNS) Tumors, Rare BRAF V600 Mutated Solid Tumors and Solid Tumors with BRAF Fusions.

2025 Strategic Objectives and Anticipated Milestones

Fore Bio is anticipating interim analyses to occur in 2025 across three monotherapy indications being evaluated in the FORTE Master Protocol:

BRAF V600 Primary Recurrent CNS Tumors: In this cohort, up to approximately 50 patients with BRAF V600 primary recurrent CNS tumors will be treated with plixorafenib. The primary endpoints of the study are overall response rate (ORR) and median duration of response (mDOR). An interim efficacy analysis from the first 25 evaluable patients is anticipated to be conducted in the third quarter of 2025. Pending a positive recommendation from the data monitoring committee, topline data from this trial would be anticipated in the second half of 2026. The company anticipates that this trial, with sufficient demonstration of safety and efficacy, would enable the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) under the Accelerated Approval pathway. In a previously conducted Phase 1/2 study of patients with MAPK inhibitor naïve BRAF V600 primary recurrent CNS tumors (n=9), plixorafenib monotherapy demonstrated a 67% ORR and a mDOR of 13.9 months, along with a favorable tolerability profile.

Rare BRAF V600 Mutated Solid Tumors: In this cohort, up to approximately 75 patients with rare BRAF V600 mutated solid tumors will be treated with plixorafenib. The primary endpoints of the study are ORR and median duration of response mDOR. An interim efficacy analysis from the first 25 evaluable patients is anticipated to be conducted in the fourth quarter of 2025. In a previously conducted Phase 1/2 study of patients with MAPK inhibitor naïve BRAF V600 mutated solid tumors (n=24), plixorafenib monotherapy demonstrated a 42% ORR and a mDOR of 17.8 months, along with a favorable tolerability profile.

Advanced Solid Tumors with BRAF Fusions: In this cohort, up to approximately 75 patients with advanced solid tumors with non-V600 BRAF fusions will be treated with plixorafenib. The primary endpoints of the study are ORR and median duration of response mDOR. An interim efficacy analysis from the first 25 evaluable patients is anticipated to be conducted in the fourth quarter of 2025. In a previously conducted Phase 1/2 study of adults with advanced solid tumors with BRAF fusions (n=14), plixorafenib monotherapy results in one complete response (with a DOR of 67.4 months), one partial response and 7 stable disease, along with a favorable tolerability profile.

Recent and Upcoming Medical Meeting Presentations

AACR 2025: In April 2025, Fore presented new circulating tumor DNA (ctDNA) results from a previously completed plixorafenib clinical trial and presented the basket study design for the ongoing global Phase 2 FORTE clinical trial at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025. Results from the plasma ctDNA analysis of over 70 plixorafenib-treated patients demonstrated a high concordance between changes in ctDNA and tissue biopsy of several BRAF mutations. The correspondence shown between changes in ctDNA and tumor size across tumor types suggests that ctDNA may be a viable surrogate marker for monitoring disease. Compared to acquired mutations driving resistance to early generation BRAF inhibitors, no new mutations in MAPK pathway genes were found following plixorafenib treatment, supporting the dimer–breaker property and novel mechanism of action of plixorafenib from the early generation BRAF inhibitors.

ASCO 2025: At the upcoming 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place May 30 – June 3 in Chicago, Fore will present the master protocol design of the ongoing global Phase 2 FORTE clinical trial.

On May 22, 2025 Step Pharma ("the Company"), the global leader in CTPS1 inhibition for targeted cancer treatment, reported that the US Food and Drug Administration (FDA) has granted orphan drug designation (ODD) to its lead candidate, dencatistat, for the treatment of T cell lymphoma, encompassing all subtypes including peripheral T cell lymphoma and cutaneous T cell lymphoma (Press release, Step Pharma, MAY 22, 2025, View Source [SID1234653318]).

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The designation highlights the significant unmet medical need in T cell lymphoma, a rare and aggressive group of blood cancers. It also recognises the potential of dencatistat as a novel, selective therapeutic option. Orphan drug designation provides incentives designed to support the development of drugs for rare diseases, including market exclusivity upon approval, tax credits for clinical trial costs, and waiver of certain FDA fees.

Andrew Parker, Chief Executive Officer of Step Pharma, commented:

"Receiving orphan drug designation from the FDA, which may confer seven years of market exclusivity for dencatistat, marks an important milestone in our mission to deliver highly selective cancer therapies for patients with difficult-to-treat cancers. T cell lymphoma remains a challenging disease with limited treatment options, and we believe CTPS1 inhibition represents a new therapeutic approach with the potential to meaningfully improve outcomes."

Dencatistat is being evaluated in a phase 1/2 clinical trial for adult patients with relapsed/refractory T or B cell lymphoma. The Company is also evaluating dencatistat in a phase 1 trial in solid tumour patients, with expansion cohorts in CTPS2-null ovarian and lung cancer planned. Additionally, a phase 1b trial in essential thrombocythaemia is expected to commence in the first half of 2025, further supporting dencatistat’s potential as a targeted therapy across multiple cancer types.

On May 22, 2025 Boehringer Ingelheim reported it will present the latest data in its robust oncology pipeline at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, including patient-reported outcomes (PRO) from the Beamion LUNG-1 study evaluating zongertinib as an orally administered targeted therapy for previously treated patients with HER2 (ERBB2)-mutant advanced non-small cell lung cancer (NSCLC) (Press release, Boehringer Ingelheim, MAY 22, 2025, View Source [SID1234653334]). In addition, new data evaluating the efficacy and safety of obrixtamig for the treatment of extrapulmonary neuroendocrine carcinomas with high or low DLL3 expression will be featured in an oral session.

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"Tackling difficult-to-treat cancers requires a multi-pronged approach, which is why we’re exploring multiple pathways to address key cancer drivers, including HER2 and DLL3, to deliver meaningful advancements for the patients who need them most," said Vicky Brown, U.S. Senior Vice President and Head of Oncology, Immunology & Eye Health, Boehringer Ingelheim. "Our data at ASCO (Free ASCO Whitepaper) underscore our generational commitment to pioneering critical innovations that address patients’ greatest needs."

Developing zongertinib for the treatment of HER2-mutant advanced NSCLC
Patient reported outcomes (N=30) from the Beamion LUNG-1 study (NCT04886804) evaluating zongertinib, showed improvements in physical functioning and disease-related symptoms in previously treated patients with HER2 (ERBB2)-mutant advanced NSCLC, identified through the following surveys:

EORTC IL46/Q168 Survey (side effect burden): 80% to 90% (24 to 27) of patients reported "not at all" or "a little" side-effect trouble across all visits.1
PRO-CTCAE: Patient-reported symptomatic adverse events assessed were in line with the previously reported safety profile of zongertinib in the Beamion LUNG-1 study; the majority of patients who reported they experienced diarrhea stated "rarely" or "occasionally".1
NSCLC Symptom Assessment Questionnaire: At weeks 15 and 27, over 50% of patients reported "no coughing at all" – a key disease-related symptom – double the proportion at baseline with remaining patients responding with "mild to moderate" coughing.1
EORTC QLQ-C30 Physical Functioning: After 15 weeks of treatment with zongertinib, participants showed a 60% improvement in physical functioning from baseline (95% CI: 6.3-12.9).1 This improvement was sustained throughout the PRO data collection period.1
Physical functioning was measured by the ability to complete strenuous activities, go on long or short walks, ability to sit in a chair (versus need to stay in bed), and need for assistance completing daily tasks.1
"In treating HER2-mutant advanced non-small cell lung cancer – a disease with limited options and a poor prognosis – patient reported outcomes are critical in understanding not only how well a treatment works, but also how it is received by patients," said Dr. Joshua K. Sabari, study investigator and Associate Professor, Department of Medicine, New York University (NYU) Grossman School of Medicine; Medical Director, Thoracic Medical Oncology, NYU Langone Health’s Perlmutter Cancer Center. "The study’s reported outcomes provide further confidence in the potential of zongertinib to have a meaningful impact on the lives of patients living with this aggressive disease."

Exploring precision medicine through DLL3 targeted therapy, obrixtamig
New data will be presented from the ongoing, Phase I dose escalation study (NCT04429087) evaluating T-cell engager, obrixtamig, in previously treated patients with extrapulmonary neuroendocrine carcinomas with high or low DLL3 expression (N=60). In the study, obrixtamig demonstrated efficacy in patients with high DLL3 expression.2

The objective response rate was 40% (95% CI: 24.6-57.7) in patients with high DLL3 expression compared to 3.3% (95% CI: 0.6-16.7) in patients with low DLL3 expression.2
The median duration of response was 7.9 months (95% CI: 6.2-not calculable [NC]) in patients with high DLL3 expression compared to 2.8 months (95% CI: NC-NC) in patients with low DLL3 expression.2
The disease control rate was 66.7% (95% CI: 48.8-80.8) in patients with high DLL3 expression compared to 26.7% (95% CI: 14.2-44.4) in patients with low DLL3 expression.2
Most treatment-related adverse events (AEs) were mild to moderate in both groups. Grade ≥3 treatment-related AEs occurred in 23.3% of patients with high DLL3 expression and 20% of those with low DLL3 expression.2
"Neuroendocrine carcinomas are a relatively rare form of cancer that are unfortunately often diagnosed at advanced stages, leading to poor outcomes for patients due to both the nature of the disease and the lack of standard of care, with limited treatment options," said Dr. Jonathan Strosberg, Professor and Medical Oncologist, Neuroendocrine Tumor Division & Department of Gastrointestinal Oncology Research Program, Moffitt Cancer Center. "DLL3 is highly expressed in neuroendocrine carcinomas, making DLL3 an important biomarker in precision medicine. Findings from this study, including a 40% objective response rate, underscore the potential of obrixtamig to produce an effective and durable response in patients with high DLL3 expression, and offer a targeted approach to treating this cancer."

An ongoing Phase II DAREON-5 trial (NCT04429087) is assessing obrixtamig in patients with relapsed/refractory DLL3-high extrapulmonary neuroendocrine carcinomas.2

Additionally, new clinical data from two early-stage trials evaluating BI 765063 and BI 770371 will be presented, strengthening Boehringer’s partnership with OSE Immunotherapeutics.

Presentations at ASCO (Free ASCO Whitepaper) 2025 from Boehringer Ingelheim’s innovative pipeline highlight vision of transforming cancer care:

Presenter

Abstract title

Presentation details

Zongertinib

Joshua Sabari

Patient-reported outcomes (PRO) evaluating physical functioning and symptoms in patients with pretreated HER2-mutant advanced non-small cell lung cancer (NSCLC): Results from the Beamion LUNG-1 trial

Poster Presentation (Abstract 8620 | Post Bd100)

May 31, 1:30 – 4:30 PM CDT
David Berz

Zongertinib in HER2-altered breast cancer: Preclinical activity and preliminary results from a phase Ia dose-escalation study

Poster Presentation (Abstract 1023 | Poster Bd 2)

June 2, 9:00 AM – 12:00 PM CDT
Alison M. Schram

Beamion PANTUMOR-1: A phase II, multicenter, multicohort, open-label trial to evaluate the efficacy and safety of the oral HER2-selective tyrosine kinase inhibitor zongertinib for the treatment of HER2-mutated or overexpressed/amplified solid tumors

Poster Presentation (Abstract TPS3187 | Poster Bd 487a)

June 2, 1:30 – 4:30 PM CDT
Obrixtamig

Jaume Capdevila

Efficacy and safety of the DLL3/CD3 T-cell engager obrixtamig in patients with extrapulmonary neuroendocrine carcinomas with high or low DLL3 expression: Results from an ongoing phase I trial

Oral Presentation (Abstract 3004)

Session: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

May 30, 3:57 – 4:09 PM CDT
Martin Wermke

DAREONTM-9, a phase Ib study of obrixtamig plus topotecan in patients (pts) with advanced small cell lung cancer (SCLC): Interim analysis results

Poster Presentation (Abstract 8094 | Poster Bd 215)

May 31, 1:30 – 4:30 PM CDT
BI 770371

Judy Wang

An open-label, phase I trial of the SIRPα monoclonal antibody, BI 770371, alone and in combination with the PD-1 inhibitor ezabenlimab in patients with advanced solid tumors

Rapid Oral Presentation (Abstract 2515)

June 1, 11:15 AM – 12:45 PM CDT
Katerin
Ingrid Rojas L

An open-label, phase Ib trial of the SIRPα inhibitor BI 765063 in combination with the PD-1 inhibitor ezabenlimab and cetuximab in patients (pts) with head and neck squamous cell carcinoma

Poster Presentation (Abstract 6019)

June 1, 11:30 AM – 1:00 PM CDT
BI 765179

Jean-Pascal H. Machiels

An open-label, phase Ib dose-expansion study to assess the efficacy of CD137/FAP agonist BI 765179 plus pembrolizumab as a first-line treatment in metastatic or incurable, recurrent programmed cell death ligand-1 (PD-L1)-positive head and neck squamous cell carcinoma (HNSCC)

Poster Presentation (Abstract TPS2684 | Poster Bd 323a)

June 2, 1:30 – 4:30 PM CDT
About non-small cell lung cancer (NSCLC)
Lung cancer claims more lives than any other cancer type3 and the incidence is set to increase to over 3 million cases worldwide by 2040.4 NSCLC is the most common type of lung cancer.5 The condition is often diagnosed at a late stage,6 and fewer than 3 in 10 patients are alive five years after diagnosis.7 People living with advanced NSCLC can experience a detrimental physical, psychological, and emotional impact on their daily lives. There remains a high unmet need for additional treatment options for people living with advanced NSCLC. Up to 4% of lung cancers are driven by HER2 mutations (or gene alterations).8 Mutations in HER2 can lead to overexpression and overactivation, which can in turn result in uncontrolled cell production, inhibition of cell death and promotion of tumor growth and spread.9

About zongertinib
Zongertinib is an investigational irreversible tyrosine kinase inhibitor (TKI) that selectively inhibits HER2 while sparing wild-type EGFR, thereby limiting associated toxicities. This orally administered, targeted therapy was granted FDA Fast Track Designation in 2023, followed by Breakthrough Therapy Designation in the U.S. and China for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 mutations and who have received prior systemic therapy. An application for accelerated approval was granted Priority Review status by the FDA in February 2025. In addition, Japan’s Pharmaceuticals and Medical Devices Agency granted Orphan Drug Designation to zongertinib.

A recent study has shown pre-clinically that the investigational compound zongertinib has potential for further clinical study in HER2 dependent solid cancers as monotherapy and as concurrent treatment with ADC therapy. In addition, zongertinib is being evaluated in Beamion LUNG-2 (NCT06151574)4, a global Phase III trial, compared to standard of care as first-line treatment in patients with unresectable, locally advanced or metastatic NSCLC who have activating HER2 TKD mutations.

About the Beamion clinical trial program
Beamion LUNG-1 (NCT04886804) is an open-label, Phase I dose escalation trial, with dose confirmation and expansion of zongertinib as monotherapy in people with advanced or metastatic solid tumors and NSCLC with activating HER2 alterations. The study has 2 parts. The first part is open to adults with different types of advanced cancer (solid tumors with changes in the HER2 gene) for whom previous treatment was not successful. The second part is open to people with advanced non-small cell lung cancer with a specific mutation in the HER2 gene. Beamion LUNG-2 is a Phase III, open label, randomized, active-controlled study in patients with unresectable, locally advanced or metastatic non-squamous NSCLC harboring HER2 TKD mutations to evaluate zongertinib compared with standard of care.

About obrixtamig
Obrixtamig is an investigational novel Immunoglobin G (IgG)-like bispecific T-cell engager designed to bind concomitantly to DLL3 on tumor cells and CD3 on T-cells.10 By creating a physical link between T-cells and tumor cells, the T-cell engager could potentially activate T-cells against DLL3-expressing tumor cells, potentially resulting in their destruction by the body’s own immune system. Activated T-cells could indirectly stimulate other immune cells to broaden the immune response against the tumor tissue.

NCT04429087 is a Phase I trial evaluating obrixtamig in patients whose tumors are positive for DLL3. The aim of the study is to determine the highest dose of obrixtamig that can be tolerated by patients before reaching the maximum tolerated dose. The study also aims to assess the side effects of obrixtamig to evaluate early evidence of antitumor activity. In addition, obrixtamig is being evaluated in additional tumor types, including an ongoing Phase II trial (DAREON-5) in patients with relapsed/refractory DLL3-high epNECs.

About extrapulmonary neuroendocrine carcinomas
Extrapulmonary neuroendocrine carcinomas (epNECs) are rare, aggressive cancers arising outside the lungs, from neuroendocrine cells present in various organs such as the gastrointestinal tract, pancreas, and others.11 Delta-like ligand 3 (DLL3) is a protein that is expressed specifically on the surface of up 77% of NECs. In normal tissue, DLL3 is minimally expressed, which makes it an ideal therapeutic target. These cancers are often diagnosed at an advanced stage, leading to poor survival rates. Like other aggressive cancers, epNECs can significantly impact patients’ physical, psychological, and emotional well-being.12 There remains a high unmet need for effective treatment options for individuals with advanced epNECs. Research is ongoing to identify molecular targets and develop new therapies.

On May 22, 2025 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported two-year follow-up data from the Phase III STARGLO study. After a median follow-up of 24.7 months, data showed a 40% improvement in overall survival (OS) for patients treated with Columvi (glofitamab-gxbm) in combination with gemcitabine and oxaliplatin (GemOx) and median OS was not reached, compared to 13.5 months for Rituxan (rituximab) plus GemOx (R-GemOx) (Press release, Genentech, MAY 22, 2025, View Source [SID1234653350]). These updated data continue to demonstrate the statistically significant and clinically meaningful survival benefit of this off-the-shelf, fixed-duration Columvi combination for people with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who have received at least one prior line of therapy and are not candidates for autologous stem cell transplant (ASCT). Data will be presented in an oral session at the 61st American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), May 30 – June 3, 2025.

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"We are encouraged that the two-year follow-up data for Columvi reinforces its potential to extend the lives of many patients where prognosis has historically been poor," said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. "These findings demonstrate the potential lasting benefits of early and effective treatment initiation with a bispecific antibody for people with relapsed or refractory disease."

"When cancer comes back or doesn’t respond to treatment, it’s devastating for patients with DLBCL given the aggressive nature of the disease," said Haifaa Abdulhaq, M.D., professor, University of California San Francisco (UCSF), director of Hematology, UCSF Fresno. "In my community practice, I’ve seen the potential of this Columvi combination to help patients start treatment quickly – providing lasting remissions and more time without ongoing therapy."

The benefit across key secondary endpoints, including progression-free survival (PFS) and complete remission (CR), was maintained for patients treated with the Columvi combination. There was a 59% reduction in the risk of disease progression or death (hazard ratio =0.41, 95% confidence interval: 0.29–0.58) and more than twice as many patients sustained a CR (58.5% vs. 25.3%). Among patients with a CR at the end of the treatment period, 89% were alive and 82% had maintained remission one year after treatment. Safety of the combination remained unchanged from the previous analysis and was consistent with the known safety profiles of the individual medicines. Patients received a higher median number of cycles of the Columvi combination (11 versus 4), due to disease progression in the R-GemOx arm. A higher rate of adverse events (AEs) was observed with the Columvi regimen. One of the most common AEs was cytokine release syndrome, which was generally low grade.

Given the wide adoption of global treatment guidelines in real-world clinical practice, there are no biological or clinical differences in DLBCL management worldwide. While second-line therapies have advanced, DLBCL can progress rapidly and many people are not candidates for, cannot tolerate, or do not have access to latest therapies. There is an urgent need for treatments that are rapidly available upon a diagnosis of relapse, that can manage the disease and improve long-term outcomes.

Based on the STARGLO data, this Columvi combination is approved in more than 30 countries for people with R/R DLBCL who are not candidates for ASCT, including countries throughout the EU. Columvi in combination with GemOx was added to the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines) as an NCCN category 1 preferred recommendation for the treatment of people with second-line DLBCL who are not intended to proceed to transplant.† Columvi monotherapy has been approved for use in R/R DLBCL after two or more prior lines of therapy in more than 60 countries worldwide.

Columvi is part of Genentech’s industry-leading CD20xCD3 bispecific antibody program. Together with the clinical development of off-the-shelf allogeneic CAR T-therapies, Genentech aims to provide tailored treatment options that suit the diverse needs, preferences, and experiences of people with blood cancers and healthcare systems.

†NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

About the STARGLO study

The STARGLO study [GO41944; NCT04408638] is a Phase III, multicenter, open-label, randomized study evaluating the efficacy and safety of Columvi (glofitamab-gxbm) in combination with gemcitabine plus oxaliplatin (GemOx) versus Rituxan (rituximab) in combination with GemOx in patients with relapsed or refractory diffuse large B-cell lymphoma who have received at least one prior line of therapy and who are not candidates for autologous stem cell transplant, or who have received two or more prior lines of therapy. Preclinical research indicated an increased antitumor effect when combining Columvi with GemOx over GemOx alone, so the STARGLO study was initiated to further explore the potential complementary effects of the treatment combination. Outcome measures include overall survival (primary endpoint), progression-free survival, complete response rate, objective response rate, duration of objective response (secondary endpoints), and safety and tolerability.

About Columvi (glofitamab-gxbm)

Columvi is a CD20xCD3 T-cell engaging bispecific antibody designed to target CD3 on the surface of T cells and CD20 on the surface of B cells. Columvi was designed with a novel 2:1 structural format. This T-cell engaging bispecific antibody is engineered to have one region that binds to CD3, a protein on T cells, a type of immune cell, and two regions that bind to CD20, a protein on B cells, which can be healthy or malignant. This dual-targeting brings the T cell in close proximity to the B cell, activating the release of cancer cell-killing proteins from the T cell. Columvi is part of Genentech’s broad and industry-leading CD20xCD3 T-cell-engaging bispecific antibody clinical development program, which aims to provide tailored treatment options that suit the diverse needs, preferences, and experiences of people with blood cancers and healthcare systems. Genentech is investigating Columvi as a monotherapy and in combination with other medicines for the treatment of diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma.

As part of Genentech’s efforts to elevate treatment standards in the earlier stages of DLBCL, where there is the best opportunity to improve long-term outcomes and prevent relapse, Columvi is also being investigated in combination with other medicines in previously untreated DLBCL in the Phase III SKYGLO study [GO44145; NCT06047080].

About Diffuse Large B-Cell Lymphoma

Diffuse large B-cell lymphoma (DLBCL) is an aggressive (fast-growing) blood cancer and is the most common form of non-Hodgkin’s lymphoma in the U.S. Approximately 160,000 people worldwide are diagnosed with DLBCL each year, with comparable incidence rates across regions. Medical practices, including pathological classification, diagnosis, staging, initial treatment and relapse management, are similarly approached worldwide. While it is generally responsive to treatment in the frontline, as many as 40% of people will relapse or have refractory disease, at which time salvage therapy options are limited and survival is short. Improving treatments earlier in the course of the disease and providing much-needed alternative options could help to improve long-term outcomes.

Columvi U.S. Indication

Columvi (glofitamab-gxbm) is a prescription medicine to treat adults with certain types of diffuse large B-cell lymphoma (DLBCL) or large B-cell lymphoma (LBCL) that has come back (relapsed) or that did not respond to previous treatment (refractory), and who have received 2 or more prior treatments for their cancer.

It is not known if Columvi is safe and effective in children.

The conditional approval of Columvi is based on response rate and durability of response. There are ongoing studies to establish how well the drug works.

What is the most important information I should know about Columvi?

Columvi can cause Cytokine Release Syndrome (CRS), a serious side effect that is common during treatment with Columvi, and can also be serious and lead to death.

Call your healthcare provider or get emergency medical help right away if you develop any signs or symptoms of CRS, including:

fever of 100.4°F (38°C) or higher
chills or shaking
fast or irregular heartbeat
dizziness or light-headedness
trouble breathing
shortness of breath
Due to the risk of CRS, you will receive Columvi on a "step-up dosing schedule".

A single dose of a medicine called obinutuzumab will be given to you on the first day of your first treatment cycle (Day 1 of Cycle 1).
You will start the Columvi step-up dosing schedule a week after the obinutuzumab dose. The step-up dosing schedule is when you receive smaller "step-up" doses of Columvi on Day 8 and Day 15 of Cycle 1. This is to help reduce your risk of CRS. You should be hospitalized during your infusion and for 24 hours after receiving the first step-up dose on Day 8. You should be hospitalized during your infusion and for 24 hours after receiving the second step-up dose on Day 15 if you experienced CRS during the first step-up dose.
You will receive your first full dose of Columvi a week after the second step-up dose (this will be Day 1 of Cycle 2).
If your dose of Columvi is delayed for any reason, you may need to repeat the "step-up dosing schedule".
If you had more than mild CRS with your previous dose of Columvi, you should be hospitalized during and for 24 hours after receiving your next dose of Columvi.
Before each dose of Columvi, you will receive medicines to help reduce your risk of CRS and infusion-related reactions.
Your healthcare provider will monitor you for CRS during treatment with Columvi and may treat you in a hospital if you develop signs and symptoms of CRS. Your healthcare provider may temporarily stop or completely stop your treatment with Columvi if you have severe side effects.

Carry the Columvi Patient Wallet Card with you at all times and show it to all of your healthcare providers. The Columvi Patient Wallet Card lists the signs and symptoms of CRS you should get emergency medical help for right away.

What are the possible side effects of Columvi?

Columvi may cause serious side effects, including:

Cytokine Release Syndrome.
Neurologic problems. Columvi can cause serious neurologic problems that may lead to death. Your healthcare provider will monitor you for neurologic problems during treatment with Columvi. Your healthcare provider may also refer you to a healthcare provider who specializes in neurologic problems. Tell your healthcare provider right away if you develop any signs or symptoms of neurologic problems, including:
headache
confusion and disorientation
difficulty paying attention or understanding things
trouble speaking
sleepiness
memory problems
numbness, tingling, or weakness of the hands or feet
dizziness
shaking (tremors)
Serious Infections. Columvi can cause serious infections that may lead to death. Your healthcare provider will monitor you for signs and symptoms of infection and treat you as needed. Tell your healthcare provider right away if you develop any signs of an infection, including: fever, chills, weakness, cough, shortness of breath, or sore throat.
Growth in your tumor or worsening of tumor related problems (tumor flare). Tell your healthcare provider if you get any of these signs or symptoms of tumor flare:
tender or swollen lymph nodes
pain or swelling at the site of the tumor
chest pain
cough
trouble breathing
The most common side effects of Columvi include: CRS, muscle and bone pain, rash, and tiredness.

The most common severe abnormal lab test results with Columvi include: decreased white blood cells, decreased phosphate (an electrolyte), increased uric acid levels, and decreased fibrinogen (a protein that helps with blood clotting).

Your healthcare provider may temporarily stop or completely stop treatment with Columvi if you develop certain side effects.

Before receiving Columvi, tell your healthcare provider about all of your medical conditions, including if you:

have an infection
have kidney problems
are pregnant or plan to become pregnant. Columvi may harm your unborn baby
Females who are able to become pregnant:

Your healthcare provider should do a pregnancy test before you start treatment with Columvi.
You should use effective birth control (contraception) during treatment and for 1 month after your last dose of Columvi. Talk to your healthcare provider about what birth control method is right for you during this time.
Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with Columvi.
are breastfeeding or plan to breastfeed. Columvi may pass into your breast milk. Do not breastfeed during treatment and for 1 month after your last dose of Columvi.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

What should I avoid while receiving Columvi?

Do not drive, operate heavy machinery, or do other dangerous activities if you develop dizziness, confusion, shaking (tremors), sleepiness, or any other symptoms that impair consciousness until your signs and symptoms go away. These may be signs and symptoms of neurologic problems.

These are not all the possible side effects of Columvi. Talk to your health care provider for more information about the benefits and risks of Columvi.

You may report side effects to the FDA at (800) FDA-1088 or View Source You may also report side effects to Genentech at (888) 835-2555.

Please see Important Safety Information, including Serious Side Effects, as well as the Columvi full Prescribing Information and Medication Guide or visit View Source

On May 22, 2025 Galmed Pharmaceuticals Ltd. (NASDAQ: GLMD) ("Galmed" or the "Company"), a clinical-stage biopharmaceutical company for cardiometabolic diseases and GI oncological indications, reported financial results for the three months ended March 31, 2025 and recent developments (Press release, Galmed Pharmaceuticals, MAY 22, 2025, View Source [SID1234653304]).

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Key Recent Developments

Announced First Time Results in Oncology Studies: Aramchol Significantly Enhances Bayer’s Regorafenib Effect in GI Cancer Models
Signed Term Sheet for the Development of Novel Semaglutide Sublingual Formulation
Raised $6.5 million since the beginning of 2025. Company’s current cash balance is $20.1 million
Financial Summary – First Quarter 2025 vs. First Quarter 2024*:

Cash and cash equivalents, short term deposits, restricted cash and marketable debt securities totaled approximately $15.9 million as of March 31, 2025, compared to approximately $15.4 million at December 31, 2024. During May 2025, the Company raised an additional $5.0 million. As a result, as of the date hereof, the Company’s current cash balance is approximately $20.1 million.
Net loss amounted to approximately $1.1 million, or $0.62 per share, for the three months ended March 31, 2025, compared to a net loss of approximately $1.3 million, or $2.76 per share, for the three months ended March 31, 2024.
Research and development expenses amounted to approximately $0.6 million for the three months ended March 31, 2025, compared to approximately $0.6 million for the three months ended March 31, 2024.
General and administrative expenses amounted to approximately $0.6 million for the three months ended March 31, 2025, compared to approximately $0.8 million for the three months ended March 31, 2024. The decrease in general and administrative expenses for the three months ended March 31, 2023 resulted primarily from a decrease in professional services expenses.
Financial income, net amounted to approximately $0.2 million for the three months ended March 31, 2025, compared to financial income of $0.1 million for the three months ended March 31, 2024.