On June 18, 2024 Immunocore Holdings plc (Nasdaq: IMCR) ("Immunocore" or the "Company"), a commercial-stage biotechnology company pioneering and delivering transformative immunomodulating medicines to radically improve outcomes for patients with cancer, infectious diseases and autoimmune diseases, reported randomization of the first patient in the PRISM-MEL-301 trial, assessing the efficacy and safety of brenetafusp (IMC-F106C; PRAME-A02), in combination with nivolumab, in first-line advanced or metastatic cutaneous melanoma (Press release, Immunocore, JUN 18, 2024, View Source [SID1234644424]).

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"We are very proud to have started the registrational program for brenetafusp, our PRAME candidate, supported by the recent promising brenetafusp monotherapy data in late-line cutaneous melanoma" said Mohammed Dar, Senior Vice President, Clinical Development, and Chief Medical Officer, Immunocore. "The PRISM-MEL-301 trial – the first Phase 3 trial for any PRAME-targeted therapy – will test whether combining brenetafusp with nivolumab may be a more effective treatment option than current standards of care for newly diagnosed metastatic or advanced cutaneous melanoma patients."

The Phase 3 trial (NCT06112314) will randomize HLA-A*02:01 positive patients with first-line, advanced or metastatic cutaneous melanoma to brenetafusp + nivolumab versus a control arm of either nivolumab or nivolumab + relatlimab, depending on country. Bristol Myers Squibb will provide nivolumab.

Professor Georgina Long, Co-Medical Director of Melanoma Institute Australia, said: "The PRISM-MEL-301 Phase 3 trial is a great example of outside-the-box scientific thinking, leveraging the immune system in a new way in the hope of beating cancer. My hope is that we can get closer to our goal of zero deaths from melanoma by conducting clinical trials with innovative drug therapies such as this."

The Company has shared the cutaneous melanoma Phase 1 data during an oral presentation at the 2024 American Society of Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on 31 May. The data showed that brenetafusp was well tolerated as monotherapy and in combination with anti-PD1, and demonstrated promising monotherapy clinical activity, including disease control rate (partial response and stable disease), progression free survival, and circulating tumor DNA molecular response.

Brenetafusp is the first PRAME x CD3 ImmTAC bispecific protein targeting an HLA-A*02:01 PRAME (PReferentially expressed Antigen in Melanoma) antigen. The Company is continuing to enroll patients into a Phase 1/2 trial in monotherapy and combination arms across multiple tumor types, including three expansion arms for patients with advanced ovarian, non-small cell lung, and endometrial cancers.

About ImmTAC molecules for cancer

Immunocore’s proprietary T cell receptor (TCR) technology generates a novel class of bispecific biologics called ImmTAC (Immune mobilizing monoclonal TCRs Against Cancer) molecules that are designed to redirect the immune system to recognize and kill cancerous cells. ImmTAC molecules are soluble TCRs engineered to recognize intracellular cancer antigens with ultra-high affinity and selectively kill these cancer cells via an anti-CD3 immune-activating effector function. Based on the demonstrated mechanism of T cell infiltration into human tumors, the ImmTAC mechanism of action holds the potential to treat hematologic and solid tumors, regardless of mutational burden or immune infiltration, including immune "cold" low mutation rate tumors.

About PRISM-MEL-301 – Phase 3 trial with brenetafusp (IMC-F106C, PRAME-A02) in 1L advanced cutaneous melanoma

The Phase 3 registrational trial will randomize HLA-A*02:01-positive patients with previously untreated advanced melanoma to brenetafusp + nivolumab versus nivolumab or nivolumab + relatlimab, depending on the country where the patient is enrolled. The trial will initially randomize to three arms: two brenetafusp dose regimens (40 mcg and 160 mcg) and control arm and will discontinue one of the brenetafusp dose regimens after an initial review of the first 60 patients randomized to the two experimental arms (90 patients randomized total). The primary endpoint of the trial is progression free survival (PFS) by blinded independent central review (BICR), with secondary endpoints of overall survival (OS) and overall response rate (ORR).

About the IMC-F106C-101 Phase 1/2 trial

IMC-F106C-101 is a first-in-human, Phase 1/2 dose escalation trial in patients with multiple solid tumor cancers including non-small cell lung cancer (NSCLC), small-cell lung cancer (SCLC), endometrial, ovarian, cutaneous melanoma, and breast cancers. The Phase 1 dose escalation trial was designed to determine the maximum tolerated dose (MTD), as well as to evaluate the safety, preliminary anti-tumor activity and pharmacokinetics of IMC-F106C (brenetafusp), a bispecific protein built on Immunocore’s ImmTAC technology, and the Company’s first molecule to target the PRAME antigen. The Company has initiated patient enrollment into four expansion arms in cutaneous melanoma, ovarian, NSCLC, and endometrial carcinomas. The IMC-F106C-101 trial is adaptive and includes the option for Phase 2 expansion, allowing for approximately 100 patients treated per tumor type in the Phase 1 and 2 expansion arms. Ph1 monotherapy continues in additional solid tumors as well as multiple combinations with standards-of-care, including checkpoint inhibitors, chemotherapy, targeted therapies, and tebentafusp.

About Cutaneous Melanoma

Cutaneous melanoma (CM) is the most common form of melanoma. It is the most aggressive skin carcinoma and is associated with the vast majority of skin cancer-related mortality. The majority of patients with CM are diagnosed before metastasis but survival remains poor for the large proportion of patients with metastatic disease. Despite recent progress in advanced melanoma therapy, there is still an unmet need for new therapies that improve first-line response rates and duration of response as well as for patients who are refractory to first-line treatments.

On June 18, 2024 Precision-Panc team at the University of Glasgow, with their Co-Sponsor, NHS Greater Glasgow & Clyde, reported the opening of the Phase II PRIMUS-006 study evaluating IMM-101, a broad-spectrum immunomodulatory agent containing heat-killed, whole cell Mycobacterium obuense, in combination with gemcitabine and pembrolizumab as first-line treatment in patients with metastatic pancreatic cancer (Press release, Immodulon Therapeutics, JUN 18, 2024, View Source [SID1234644423]). The PRIMUS-006 study is part of the Precision-Panc Platform master protocol program, which is Co-Sponsored by NHS Greater Glasgow & Clyde and the University of Glasgow and co-ordinated by the Glasgow Oncology Clinical Trials Unit. PRIMUS-006 is endorsed by Cancer Research UK (CRUK Reference: A31505).

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The study is funded by Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, U.S.A., through its investigator-initiated program with provision of study drug and financial support.The study is also funded by Immodulon Therapeutics Ltd through its investigator-initiated program with provision of study drug and financial support for the study.

"The opening of the Phase II PRIMUS-006 study is an important milestone in the pursuit to develop new treatment options to improve the overall outcomes in patients diagnosed with pancreatic cancer," said Professor David Chang, principal investigator and professor of surgical oncology & honorary consultant pancreatic surgeon, Wolfson Wohl Cancer Research Centre, University of Glasgow and Glasgow Royal Infirmary. "The selection of IMM-101 to comprise part of the triplet combination reflects its potential to enhance anti-tumour activity alongside gemcitabine and pembrolizumab in patients with first-line metastatic pancreatic cancer," said Professor Jeff Evans of the University of Glasgow and Honorary Consultant in Medical Oncology at the Beatson West of Scotland Cancer Centre, Glasgow.

Pancreatic ductal adenocarcinoma (PDAC) tends to be poorly immunogenic with diminished antigen presentation and a highly immunosuppressive tumour micro-environment that further impedes the functional activation of cytotoxic T lymphocytes. Based on the ability of gemcitabine to enhance the expression of antigen-presenting molecules, its use in combination with IMM-101, a broad-spectrum immunomodulator with potential to sensitize pancreatic cancers to immune checkpoint inhibition, and pembrolizumab, MSD’s anti-PD-1 therapy, this novel combination has the potential to enhance anti-tumour efficacy in patients with first-line pancreatic cancer.

"This is an exciting opportunity to be part of a high caliber pancreatic cancer research program and reflects the potential of IMM-101 to become a backbone therapy in immunologically cold tumours by enhancing the efficacy of existing anti-cancer treatment options, including chemotherapy and checkpoint inhibitors," said Josefine Roemmler-Zehrer, MD, Associate Professor, and Chief Medical Officer of Immodulon. "We look forward to working with the Co-Sponsors NHS Greater Glasgow & Clyde and University of Glasgow, MSD and other key collaborators to support this study and advance our efforts to bring IMM-101 closer to patients diagnosed with pancreatic cancer and other solid tumours."

The Phase II PRIMUS-006 study is a single-arm clinical study evaluating IMM-101, gemcitabine and pembrolizumab as first-line combination triplet therapy in patients diagnosed with metastatic pancreatic cancer who are deemed not sufficiently fit enough to tolerate treatment consisting of two or more cytotoxic agents. As the overall objective of the study is to enhance the anti-tumour activity of immunotherapy, the primary endpoint of the study is the objective response rate as defined by RECIST 1.1. Key secondary endpoints include safety and tolerability, evaluation of progression-free survival, disease control rate and overall survival. Up to 50 patients with metastatic pancreatic ductal adenocarcinoma will be treated in the study from approximately 15-20 hospital sites in the United Kingdom.

About Pancreatic Ductal Adenocarcinoma (PDAC)

PDAC is the third most common cause of cancer death in the developed world. Approximately 50% of patients present with metastatic disease and most of the patients who present with resectable or locally advanced inoperable disease ultimately develop metastatic disease.

Gemcitabine monotherapy has modest clinical benefit and a marginal survival advantage in patients with metastatic PDAC. Better response rates and survival can be achieved with the FOLFIRINOX regimen, and with the addition of nab-paclitaxel to gemcitabine.

Nevertheless, overall survival remains disappointing with these combination cytotoxic chemotherapy regimens.
Furthermore, many patients are not fit enough to tolerate these combination regimens, and these patients are invariably excluded from participation in clinical trials because of lower performance status. Consequently, these patients represent a significant unmet clinical need and are in urgent need of novel therapeutic approaches.

About IMM-101

IMM-101 is a systemic, broad-spectrum immunomodulator containing heat-killed, whole cell Mycobacterium obuense, capable of generating a broad systemic innate and adaptive type 1 immune response with potential to treat immunologically ‘cold’ cancers, like pancreatic cancer. In the Phase II IMAGE-1 Study of IMM-101 in combination with gemcitabine, clinical data indicate that IMM-101 is well-tolerated and effective and that it has the potential as a first-line treatment to prolong progression-free survival in patients with advanced pancreatic ductal adenocarcinoma (PDAC) when compared to gemcitabine alone. The study data also suggest a beneficial effect on survival in patients with metastatic PDAC. Immodulon is currently prioritizing the initiation of a Bayesian adaptive pivotal study for IMM-101 in PDAC that can be expanded to evaluate IMM-101 in other immunologically ‘cold’ tumours across multiple parallel arms.

On June 18, 2024 FibroGen, Inc. (NASDAQ: FGEN) reported it will host the second part of its virtual KOL investor event series on Wednesday, June 26, 2024 at 10:00 AM ET. To register, click here (Press release, FibroGen, JUN 18, 2024, View Source [SID1234644422]).

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The event will feature Rahul Aggarwal, M.D. (University of California San Francisco), who will discuss the unmet need and evolving treatment landscape for prostate cancer, as well as the clinical development program for FG-3246* (also known as FOR46), a CD46 targeting antibody-drug conjugate (ADC) with first-in-class potential for the treatment of metastatic castration-resistant prostate cancer (mCRPC). The initiation of a Phase 2 monotherapy trial in mCRPC is expected in the second half of 2024.

The event will additionally review data from the Phase 1b/2 study evaluating FG-3246 in combination with enzalutamide in mCRPC presented at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) meeting.

A live question and answer session will follow the formal presentation.

This series is intended for investor audiences only.

About Rahul Aggarwal, MD
Rahul Aggarwal, MD is a Professor of Medicine and Thomas Perkins Distinguished Professor of Cancer Research at the University of California San Francisco. He is the Associate Director for Clinical Research in the UCSF Helen Diller Family Comprehensive Cancer Center and the Program Leader for the Genitourinary Oncology program. He specializes in translational and clinical research in prostate cancer, with a particular emphasis on the development of novel therapeutic and imaging modalities for men with advanced prostate cancer. He has led numerous phase 1, 2, and 3 clinical trials in prostate cancer across a number of treatment modalities including small molecule targeted therapies, radioligand therapies, antibody-drug conjugates, and bi-specific T cell engagers.

About FG-3246
FG-3246 (FOR46) is a potential first-in-class fully human antibody-drug conjugate (ADC), exclusively in-licensed from Fortis Therapeutics, and is being developed by FibroGen for metastatic castration-resistant prostate cancer and potentially other tumor types. FG-3246 binds to an epitope of CD46, a cell receptor target, that induces internalization upon antibody binding, is present at high levels in prostate cancer and other tumor types and demonstrates very limited expression in most normal tissues. FG-3246 is comprised of an anti-CD46 antibody, YS5, linked to the anti-mitotic agent, MMAE, which is a clinically and commercially validated ADC payload. FG-3246 has demonstrated anti-tumor activity in both preclinical and clinical studies. FG-3246 is currently in an ongoing Phase 1b/2 study being conducted at UCSF as an investigator-sponsored trial to evaluate FG-3246 in combination with enzalutamide. An additional investigator-sponsored radiopharmaceutical marker trial using a zirconium-89 positron emission tomography (PET) tracer for CD46 that utilizes the YS5 antibody is also underway at UCSF. The initiation of the Phase 2 monotherapy trial in metastatic castration-resistant prostate cancer is anticipated in the second half of 2024. FG-3246 is an investigational drug and not approved for marketing by any regulatory authority.

On June 18, 2024 Day One Biopharmaceuticals (Nasdaq: DAWN) ("Day One" or the "Company"), a commercial-stage biopharmaceutical company dedicated to developing and commercializing targeted therapies for people of all ages with life-threatening diseases, reported it has entered into an exclusive licensing agreement (the Agreement) with MabCare Therapeutics (MabCare) for MTX-13, a novel ADC targeting protein-tyrosine kinase 7 (PTK7) (Press release, Day One, JUN 18, 2024, View Source [SID1234644421]). Pursuant to the terms of the Agreement, Day One has exclusive rights to develop, manufacture, and commercialize MTX-13 worldwide, excluding Greater China.

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In April 2024, the U.S. Food and Drug Administration (FDA) cleared the investigational new drug (IND) application for MTX-13, which going forward will be identified as DAY301. In pre-clinical studies, DAY301 showed antitumor activity in a wide range of solid tumors.

"Our priorities for 2024 are to successfully launch OJEMDATM (tovorafenib), to advance our existing programs and to expand our pipeline by in-licensing clinical-stage assets that have the potential to transform outcomes for patients of all ages living with cancers," said Jeremy Bender, Ph.D., chief executive officer of Day One. "We are excited by the opportunity presented by DAY301, and we believe we have the right team in place to develop the program to its full potential."

DAY301 targets PTK7, a highly-conserved, catalytically inactive transmembrane protein that is overexpressed in multiple adult cancers, including esophageal, ovarian, lung, and endometrial cancer, as well as pediatric cancers such as neuroblastoma, rhabdomyosarcoma and osteosarcoma. PTK7 has limited expression in normal tissues or organs, making it an attractive target for therapeutic development.

"The addition of DAY301 to our pipeline strategically fits our mission of advancing both pediatric and adult medicines in areas of unmet need with equal urgency," said Dr. Samuel Blackman, co-founder and head of research and development at Day One. "We believe the linker-payload technology embodied in DAY301 will overcome the limitations of earlier PTK7-targeted ADCs, giving us a potential first-in-class drug against a clinically-validated target. We are excited to add this program to Day One and will look to enter the clinic in the coming months."

Under the terms of the licensing agreement, MabCare will receive $55 million upfront, and is eligible to receive an additional $1.152 billion in development, regulatory and commercial success-based milestones, plus low-to-mid single-digit royalties on net sales outside of Greater China. Day One expects the first patient to be dosed in the Phase I study in the fourth quarter of 2024 or first quarter of 2025.

On June 18, 2024 CytomX Therapeutics, Inc. (Nasdaq: CTMX), a leader in the field of masked, conditionally activated biologic therapeutics, reported that Sean McCarthy, D.Phil., chief executive officer and chairman, will participate in a fireside chat at the H.C. Wainwright 2nd Annual Immune Cell Engager Virtual Conference on Tuesday, June 25, 2024, at 2:00 p.m. ET (Press release, CytomX Therapeutics, JUN 18, 2024, View Source [SID1234644420]).

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A live webcast of the presentation will be available on the Events and Presentations page of CytomX’s website at www.cytomx.com. In addition, management will be available for one-on-one meetings with investors who are registered to attend the conference.