On September 11, 2023 Immunocore Holdings Plc (Nasdaq: IMCR), a commercial-stage biotechnology company pioneering the development of a novel class of T cell receptor (TCR) bispecific immunotherapies designed to treat a broad range of diseases, including cancer, infectious diseases and autoimmune conditions, reported that management will present at the following investor conferences in September (Press release, Immunocore, SEP 11, 2023, View Source [SID1234635067]):

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H.C. Wainwright Healthcare Conference
Fireside Chat: Monday, September 11, 2023, at 2:30 p.m. EDT
Morgan Stanley Healthcare Conference
Fireside Chat: Tuesday, September 12, 2023, at 5:30 p.m. EDT
Baird Healthcare Conference
1×1 and small group meetings: Wednesday, September 13, 2023
2023 Cantor Global Healthcare Conference
Fireside Chat: Thursday, September 28, 2023, at 8:00 a.m. EDT

Where relevant, the presentations will be webcast live and can be accessed by visiting ‘Events’, under ‘News & Events’, via the ‘Investors’ section of Immunocore’s website at www.immunocore.com. Following the events, a replay of the presentations will be made available for a limited time.

On September 11, 2023 Moderna, Inc. (NASDAQ: MRNA, "Moderna") and Immatics N.V. (NASDAQ: IMTX, "Immatics"), a clinical-stage biopharmaceutical company active in the discovery and development of T cell-redirecting cancer immunotherapies, reported a strategic research and development collaboration to pioneer novel and transformative therapies for cancer patients with high unmet medical need (Press release, Immatics, SEP 11, 2023, View Source [SID1234635065]). This broad multi-platform collaboration will leverage the deep scientific expertise and core operational capabilities of both companies, combining Immatics’ TCR platform with Moderna’s cutting-edge mRNA technology, and span various therapeutic modalities including bispecifics, cell therapy and cancer vaccines.

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The strategic R&D collaboration between Moderna and Immatics focuses on three pillars:

Applying Moderna’s mRNA technology for in vivo expression of Immatics’ next-generation, half-life extended TCR bispecifics (TCER) targeting cancer-specific HLA-presented peptides.
Enabling the discovery and development of novel mRNA-based cancer vaccines by leveraging Moderna’s deep knowledge of mRNA science and customized information from Immatics’ wealth of tumor and normal tissue data included in the target discovery platform XPRESIDENT and its bioinformatics and AI platform XCUBE.
Evaluating Immatics’ IMA203 TCR-T therapy targeting PRAME in combination with Moderna’s PRAME mRNA-based cancer vaccine. The collaboration contemplates conducting preclinical studies and a Phase 1 clinical trial evaluating the safety and efficacy of the combination with the objective of further enhancing IMA203 T cell responses.

"We are excited to embark on this strategic collaboration with Immatics, a pioneer in developing innovative cancer immunotherapies. This partnership presents a groundbreaking opportunity to leverage our mRNA technology alongside Immatics’ TCR platform, potentially diversifying and augmenting the way we approach cancer treatment. We believe this collaboration will accelerate the development of novel oncology therapies and bring us one step closer to providing significant benefits for patients with high unmet medical needs," said Rose Loughlin, Ph.D., Moderna’s Senior Vice President for Research and Early Development.

"We are thrilled to join forces with Moderna in our quest to pioneer innovative and transformative therapies to combat cancer. We believe Immatics’ cancer target and TCR platforms, along with Moderna’s cutting-edge mRNA technology, represent a powerful combination that has the potential to deliver meaningful benefits to cancer patients," said Toni Weinschenk, PhD, Chief Innovation Officer at Immatics. "The rapid advancement of our first 2 TCER programs into the clinic, with additional TCER compounds fueling our pre-clinical pipeline, underscores our commitment to develop innovative therapeutics. We are confident that we can explore the optimal delivery of TCER molecules through this collaboration to maximize clinical benefit in a broad patient population," added Carsten Reinhardt, MD, PhD, Chief Development Officer of Immatics.

About the Collaboration
Under the terms of the agreement, Immatics will receive an upfront payment of $120 million. Immatics will also receive research funding and is eligible to receive development, regulatory, and commercial milestone payments that could exceed $1.7 billion. Immatics is also eligible to receive tiered royalties on global net sales of TCER products and certain vaccine products that are commercialized under the agreement. Under the agreement, Immatics has an option to enter into a global profit and loss share arrangement for the most advanced TCER.

Moderna will lead the clinical development and commercialization of cancer vaccines and TCER therapeutics resulting from the collaboration. Immatics will be responsible for conducting the preclinical studies and a potential Phase 1 clinical trial investigating IMA203 TCR-T in combination with the PRAME mRNA vaccine to further enhance IMA203 T cell responses. Each party will retain full ownership of its investigational PRAME compound, and the parties will fund the clinical study on a cost sharing basis.

Within the collaboration, preclinical activities conducted by Immatics will be managed by the Immatics Discovery Unit, a recently created internal division at Immatics integrating its technology platforms into one interdisciplinary team focused on all early-stage preclinical pipeline and collaboration programs.

The collaboration is subject to customary antitrust clearance in the United States.

On September 11, 2023 GSK plc (LSE/NYSE: GSK) reported that the Ministry of Health, Labour and Welfare (MHLW), Japan, has accepted for review a new drug application (NDA) for momelotinib, a potential new medicine with a differentiated mechanism of action that may address the significant medical needs of myelofibrosis patients, especially those with anaemia (Press release, GlaxoSmithKline, SEP 11, 2023, View Source [SID1234635064]). The NDA is based on data from the pivotal phase III trials SIMPLIFY-1 and MOMENTUM.

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Myelofibrosis is a blood cancer that can lead to splenomegaly (enlarged spleen); constitutional symptoms such as fatigue, night sweats, and bone pain; and severely low blood counts, including anaemia and thrombocytopenia.[1],[2],[3] About 70% of patients diagnosed with primary myelofibrosis and about half of patients diagnosed with secondary myelofibrosis in Japan have moderate to severe anaemia at the time of diagnosis, and nearly all patients are estimated to develop anaemia over the course of the disease.[4],[5],[6],[7],[8],[9] Patients who are transfusion dependent have a poor prognosis and shortened survival.[10],[11],[12],[13],[14],[15],[16],[17],[18]

Momelotinib is not currently approved in any market.

About momelotinib

Momelotinib has a differentiated mechanism of action, with inhibitory ability along three key signalling pathways: Janus kinase (JAK) 1, JAK2, and activin A receptor, type I (ACVR1).[19],[20],[21],[22] Inhibition of JAK1 and JAK2 may improve constitutional symptoms and splenomegaly.[19],[21],[22] Additionally, inhibition of ACVR1 leads to a decrease in circulating hepcidin, which is elevated in myelofibrosis and contributes to anaemia.[19],[20],[21],[22]

About myelofibrosis

Myelofibrosis is a rare blood cancer that disrupts the body’s normal production of blood cells as a result of dysregulated JAK-signal transducer and activator of transcription protein signalling. The clinical hallmarks of myelofibrosis are progressive splenomegaly (enlarged spleen), anaemia and debilitating symptoms attributable to ineffective hematopoiesis and excessive production of proinflammatory cytokines.[23] Myelofibrosis patients with anaemia require additional supportive care, including transfusions, and have poor outcomes.[24],[25] Myelofibrosis affects approximately 1 in 500,000 people worldwide, with up to 5,000 patients impacted in Japan.[10],[19],[26],[27]

About the pivotal SIMPLIFY-1 clinical trial

SIMPLIFY-1 was a multicentre randomised, double-blind, phase III study that compared the safety and efficacy of momelotinib to ruxolitinib in patients with myelofibrosis who had not received prior treatment with a JAK inhibitor. SIMPLIFY-1 met its primary endpoint, demonstrating non-inferiority of momelotinib to ruxolitinib in spleen volume response (reduction by 35% or greater), and substantial improvements in transfusion independence rates.[28],[29]

About the pivotal MOMENTUM clinical trial

MOMENTUM was a global, randomised, double-blind phase III clinical trial of momelotinib (MMB) versus danazol (DAN) in patients with myelofibrosis who were symptomatic and anaemic and had been previously treated with an approved JAK inhibitor. The MOMENTUM trial met all its primary and key secondary endpoints, with respect to splenic response, constitutional symptoms and transfusion independence. Results from the 24-week treatment period were presented at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting and subsequently published in The Lancet.[22] ,[30]

On September 11, 2023 Day One Biopharmaceuticals (Nasdaq: DAWN) ("Day One" or the "Company"), a clinical-stage biopharmaceutical company dedicated to developing and commercializing targeted therapies for people of all ages with life-threatening diseases, reported the recently completed submission of the rolling New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for tovorafenib as a monotherapy in relapsed or progressive pediatric low-grade glioma (pLGG) (Press release, Day One, SEP 11, 2023, View Source [SID1234635063]). The Company anticipates the FDA will file the rolling NDA by mid-November 2023.

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pLGG is the most common brain tumor diagnosed in children, with patients suffering profound tumor and treatment-associated morbidities that can impact their life trajectory over the long term. For the majority of patients in the relapsed setting, there is no standard of care and no approved therapies.

"We believe that tovorafenib, if approved, could change the treatment landscape for children living with this chronic and relentless disease," said Jeremy Bender, Ph.D., chief executive officer of Day One. "The NDA submission of tovorafenib is a significant milestone for Day One and an important step towards bringing a potential new targeted therapy to children with brain cancer."

The Company initiated the rolling submission of the NDA in May 2023 based on data from the FIREFLY-1 trial with a data cutoff as of December 22, 2022. An updated Clinical Study Report (CSR) was submitted to the FDA with an additional six months of safety and efficacy data through June 5, 2023.

FIREFLY-1 is an open-label, pivotal Phase 2 trial, which treated a total of 137 patients across two study arms. Arm 1 evaluated tovorafenib in 77 patients as a once-weekly monotherapy in patients aged 6 months to 25 years with relapsed or progressive pLGG. The primary endpoint of the trial is ORR by Response Assessment for Neuro-Oncology High-Grade Glioma (RANO-HGG) criteria. Secondary endpoints include ORR by Response Assessment in Pediatric Neuro-Oncology Low-Grade Glioma (RAPNO-LGG), progression-free survival (PFS), duration of response (DOR), time to response, clinical benefit rate and safety. The NDA submission also includes an exploratory analysis of ORR by Response Assessment for Neuro-Oncology Low-Grade Glioma (RANO-LGG). All data have been assessed by a blinded Independent Review Committee (IRC).

Updated FIREFLY-1 Data Demonstrate Consistent and Durable Response

New data from the FIREFLY-1 trial, with a data cutoff of June 5, 2023, are described below. Detailed data will be presented at an upcoming medical conference.

RANO-HGG (n=69 evaluable) data, the primary endpoint of the trial:

•
67% ORR (complete response (CR) + partial response (PR))

•
93% clinical benefit rate (CBR) (CR + PR + stable disease (SD))

•
17% (n=12) CR

•
49% (n=34) PR

•
26% (n=18) SD

•
At the time of data cutoff, the median duration of response (DOR) based on RANO-HGG criteria was 16.6 months (95% CI: 11.6, not estimable)

Among a total of 77 treated patients:

•
The median duration of tovorafenib treatment was 15.8 months, with 66% (n=51) of patients on treatment at the time of data cutoff

Safety data, based on the 137 patients treated in both Arm 1 and Arm 2 of FIREFLY-1, indicated monotherapy tovorafenib to be generally well-tolerated. The vast majority of adverse events were Grade 1 or Grade 2, with most common side effects reported related to tovorafenib being change in hair color (76%), fatigue (44%), maculopapular rash (41%), dry skin (33%), and dermatitis acneiform (30%). The most commonly reported treatment-related lab abnormalities were CPK elevation, LDH elevation, anemia, hypophosphatemia and AST elevation. Nearly all of the lab abnormalities had no clinical manifestations and did not require clinical intervention or change in study treatment.

The NDA submission also included the evaluation of responses by RAPNO-LGG and RANO-LGG. Those results include:

RAPNO-LGG (n=76 evaluable) data, a key secondary endpoint of the trial:

•
51% ORR (CR + PR + minor response (MR))

•
82% CBR (CR+ PR + MR + SD)

•
37% (n=28) PR

•
14% (n=11) MR

•
30% (n=23) SD

•
At the time of data cutoff, the median DOR based on RAPNO-LGG criteria was 13.8 months (95% CI: 11.3, not estimable)

RANO-LGG (n=76 evaluable) data, an exploratory analysis of the trial:

•
53% ORR (CR + PR + MR)

•
83% CBR (CR + PR + MR + SD)

•
26% (n=20) PR

•
26% (n=20) MR

•
30% (n=23) SD

•
At the time of data cutoff, the median DOR based on RANO-LGG criteria was 14.4 months (95% CI: 11.0, not estimable)

Tovorafenib was granted Rare Pediatric Disease Designation for relapsed or progressive pLGG and, as such, may qualify for receipt of a priority review voucher, if tovorafenib is approved by the FDA in this indication. Based on Day One’s current operating plan, management believes it has sufficient capital resources to fund anticipated operations into 2026.

About Pediatric Low-Grade Glioma

Pediatric low-grade glioma (pLGG) is the most common brain tumor diagnosed in children, accounting for 30% – 50% of all central nervous systems tumors. BRAF wild-type fusions are the most common cancer-causing genomic alterations in pLGG. These genomic alterations are also found in severe adult and pediatric solid tumors.

Pediatric low-grade glioma can impact a child’s health in many ways depending on tumor size and location, including vision loss and motor dysfunction. There are no approved therapies for the vast majority of patients with pLGG, and current treatment approaches are associated with potential acute and life-long adverse effects. While most children with pLGG survive their cancer, children who do not achieve remission following surgery may face years of increasingly aggressive therapies. Due to the indolent nature of pLGG, patients generally receive multiple years of systemic therapy.

About FIREFLY-1

FIREFLY-1 is evaluating tovorafenib as once-weekly monotherapy in patients aged 6 months to 25 years with relapsed or progressive pLGG harboring a known activating BRAF alteration. The trial is being conducted in collaboration with the Pacific Pediatric Neuro-Oncology Consortium (PNOC). The primary endpoint is overall response rate (ORR), defined as the proportion of patients with confirmed response based upon RANO-HGG criteria. Secondary and exploratory endpoints include the overall response rate based on RAPNO-LGG criteria, RANO-LGG criteria and volumetric analyses, progression-free survival, safety, functional outcomes, and quality of life measures. RANO-HGG, RANO-LGG and RAPNO-LGG are assessed by blinded independent central review. Additional information about FIREFLY-1 may be found at ClinicalTrials.gov, using Identifier NCT04775485.

About the Pacific Pediatric Neuro-Oncology Consortium

The Pacific Pediatric Neuro-Oncology Consortium (PNOC) is an international consortium with study sites within the United States, Canada, Europe and Australia dedicated to bringing new therapies to children and young adults with brain tumors.

About Tovorafenib

Tovorafenib is an investigational, oral, brain-penetrant, highly-selective type II RAF kinase inhibitor designed to target a key enzyme in the MAPK signaling pathway, which is being investigated in primary brain tumors or brain metastases of solid tumors. Tovorafenib has been studied in over 325 patients to date. Currently tovorafenib is under evaluation in a pivotal Phase 2 clinical trial (FIREFLY-1) among pediatric, adolescent and young adult patients with relapsed or progressive pLGG, which is an area of considerable unmet need with no approved therapies for the vast majority of patients. Tovorafenib is also being evaluated alone or as a combination therapy for adolescent and adult patient populations with recurrent or progressive solid tumors with MAPK pathway aberrations (FIRELIGHT-1).

Tovorafenib has been granted Breakthrough Therapy and Rare Pediatric Disease designations by the U.S. Food and Drug Administration (FDA) for the treatment of patients with pLGG harboring an activating RAF alteration. Tovorafenib has also received Orphan Drug designation from the FDA for the treatment of malignant glioma, and from the European Commission (EC) for the treatment of glioma.

On September 11, 2023 CymaBay Therapeutics, Inc. (Nasdaq: CBAY), a clinical-stage biopharmaceutical company focused on developing innovative therapies for liver and other chronic diseases with high unmet medical need, reported that it has commenced an underwritten public offering of an aggregate of $150 million of its common stock and pre-funded warrants (Press release, CymaBay Therapeutics, SEP 11, 2023, View Source [SID1234635062]). All shares of common stock and pre-funded warrants to be sold in the offering will be offered by CymaBay. CymaBay intends to grant the underwriters a 30-day option to purchase up to an aggregate of an additional 15% of the shares of its common stock offered in the public offering, including shares of common stock underlying the pre-funded warrants. The offering is subject to market and other conditions, and there can be no assurance as to whether or when the offering may be completed, or as to the actual size or terms of the offering. CymaBay anticipates using the net proceeds from the offering to fund ongoing development of seladelpar, including clinical trials targeting market expansion, and for working capital and general corporate purposes.

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Piper Sandler, Raymond James, Cantor and LifeSci Capital are acting as the joint book-running managers for the offering. BTIG is acting as the lead manager for the offering.

The securities described above are being offered by CymaBay pursuant to a shelf registration statement previously filed with and declared effective by the Securities and Exchange Commission (the "SEC"). A preliminary prospectus supplement related to the offering will be filed with the SEC and will be available on the SEC’s website at www.sec.gov. Copies of the preliminary prospectus supplement and the accompanying prospectus relating to this offering may be obtained, when available, from: Piper Sandler & Co., Attention: Prospectus Department, 800 Nicollet Mall, J12S03, Minneapolis, Minnesota 55402, by telephone at (800) 747-3924, or by email at [email protected]; Raymond James & Associates, Inc., Attention: Equity Syndicate, 880 Carillon Parkway, St. Petersburg, Florida 33716, by telephone at (800) 248-8863, or by e-mail at [email protected]; Cantor Fitzgerald & Co., Attention: Capital Markets, 110 East 59th Street, 6th Floor, New York, New York 10022, or by e-mail at [email protected]; or LifeSci Capital LLC, Attention: Syndicate Prospectus Department, 250 West 55th Street, 34th Floor, New York, NY 10019, by email at [email protected] or by telephone at (646) 876-5059.

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 state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.