On November 2, 2023 Pfizer Inc. (NYSE: PFE) reported that it will present its latest data showcasing advances in the treatment of hemophilia, sickle cell disease, and blood cancers at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in San Diego from December 9-12 (Press release, Pfizer, NOV 2, 2023, View Source [SID1234636836]). These data from 39 presentations represent continued innovation and advancement in hemophilia including pivotal findings for Pfizer’s novel anti-tissue factor pathway inhibitor (anti-TFPI) candidate marstacimab and the latest findings on a next-generation investigational treatment for sickle cell disease (SCD) in GBT021601 (GBT601). Pfizer will also present the latest research in blood cancer, including for ELREXFIO (elranatamab-bcmm), a BCMA-directed bispecific antibody recently approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

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"Pfizer has been advancing science in hematology for more than 30 years, starting with the introduction of recombinant factor replacement therapy, which became the standard of care for people living with hemophilia. This year at ASH (Free ASH Whitepaper) we will deliver five oral presentations including the latest clinical findings from our hemophilia programs and exciting data from the GBT601 program in sickle cell disease, representing progress in our unrelenting efforts to address the broad spectrum of patient needs," said Sonal Bhatia, M.D., Chief Medical Officer, Rare Disease, Pfizer. "The findings reflect the company’s scientific capabilities and use of translational science to potentially offer improved treatment options to help people living with these rare diseases."

"During ASH (Free ASH Whitepaper), we are pleased to present new clinical and real-world data in multiple myeloma from our broad development program for ELREXFIO, following recent FDA accelerated approval. This includes extended efficacy and safety results from MagnetisMM-3, highlighting sustained clinical efficacy and no new safety signals after 20 months of follow-up," said Chris Boshoff, Chief Oncology Research and Development Officer and Executive Vice President, Pfizer. "These data continue to support the potential of ELREXFIO as the next standard of care for patients with advanced multiple myeloma."

Highlights from company-sponsored abstracts include:

Six presentations from our hemophilia pipeline, including the first presentation of primary results from the non-inhibitor cohort of the pivotal Phase 3 BASIS clinical trial evaluating marstacimab in people living with hemophilia A or B. Additionally, four-year data from Pfizer’s Phase 1/2 study of investigational gene therapy giroctocogene fitelparvovec in adults living with severe hemophilia A will be presented.
Fourteen abstracts focused on the treatment of SCD, including Phase 2a safety, efficacy, and pharmacodynamic data from the ongoing Phase 2/3 clinical trial study of GBT601. In addition, long-term safety and efficacy findings on voxelotor (over four years follow-up) will be presented as well as data illustrating insights into the experience of SCD patients and their caregivers through a social media listening study.
Nineteen abstracts from our blood cancer portfolio, including six which continue to support the use of ELREXFIO, a B-cell maturation antigen (BCMA)-CD3-directed bispecific antibody immunotherapy, in patients with RRMM. This includes extended findings from MagnetisMM-3 cohort A (~20 months median follow-up) and a pooled analysis of efficacy and safety in Black patients with RRMM from MagnetisMM-1, MagnetisMM-3, and MagnetisMM-9, reinforcing Pfizer’s commitment to health equity.
A complete list of Pfizer-sponsored accepted abstracts is available here.

Key Pfizer-sponsored oral presentations at ASH (Free ASH Whitepaper) 2023 include:

Predictive Biomarker Analysis from the GBT021601 Survival Study in Townes Sickle Mice (Abstract #14)

Pochron M

Saturday, December 9, 9:30 – 11:00 AM PST

Presentation Time: 9:45 AM PST

Efficacy and Safety of the Anti-Tissue Factor Pathway Inhibitor Marstacimab in Participants with Severe Hemophilia without Inhibitors: Results from the Phase 3 Basis Trial (Abstract #285)

Matino D

Saturday, December 9, 4:00-5:30 PM PST

Presentation Time: 4:30 PM PST

Preliminary Results from a Multicenter Phase 2/3 Study of Next-Generation HbS Polymerization Inhibitor GBT021601 for the Treatment of Patients with Sickle Cell Disease (Abstract #274)

Saraf S

Saturday, December 9, 4:00 – 5:30 PM PST

Presentation Time: 4:45 PM PST

Understanding the Experiences of Patients with Sickle Cell Disease and their Caregivers by Social Media Listening in the UK (Abstract #1057)

Shastri O

Monday, December 11, 4:30 – 6:00 PM EST

Presentation Time: 4:30 PM PST

Four-Year Follow-up of the Alta Study, a Phase 1/2 Study of Giroctocogene Fitelparvovec (PF-07055480/SB-525) Gene Therapy in Adults with Severe Hemophilia Α (Abstract #1054)

Leavitt A

Monday, December 11, 2023, 4:30 PM – 6:00 PM PST

Presentation Time: 5:15 PM

About Hemophilia

Hemophilia is a family of rare genetic blood diseases caused by a clotting factor deficiency (FVIII in hemophilia A, FIX in hemophilia B) which prevents normal blood clotting. Hemophilia is often diagnosed in early childhood and impacts more than 400,000 people worldwide.1 The inability of the blood to clot properly can increase the risk of painful bleeding inside the joints and other serious or even life-threatening bleeding. People living with hemophilia can suffer permanent joint damage following repeated bleeding episodes.1,2

For decades, the most common treatment approach for hemophilia A and B has been factor replacement therapy, which replaces the missing clotting factors. Factor replacement therapies increase the amount of clotting factor in the body to levels that improve clotting, resulting in less bleeding; however, they must be administered by IV infusion on a regular basis.2,3 Approximately 25-30% of people with hemophilia A and 3-5% of people with hemophilia B are unable to continue taking factor replacement therapies because they develop inhibitors to FVIII and FIX.4,5

About Sickle Cell Disease

Sickle cell disease (SCD) is a lifelong, debilitating inherited blood disorder characterized by hemolytic anemia, which drives vascular inflammation, acute pain crises and progressive end organ damage. Acute pain crisis, or vaso-occlusive crisis (VOC), occurs when sickled red blood cells, white blood cells and platelets stick to the inflamed lining of blood vessels leading to vascular occlusion, tissue ischemia and pain. Complications of SCD begin in early childhood and are associated with shortened life expectancy. Early intervention and treatment of SCD have shown potential to reduce symptoms, events, long-term organ damage, and extend life expectancy. Historically, there has been a high unmet need for therapies that address SCD and its acute and chronic complications. SCD occurs particularly among those whose ancestors are from sub-Saharan Africa, though it also occurs in people of Hispanic, South Asian, Southern European, and Middle Eastern ancestry.

About Multiple Myeloma

Multiple myeloma (MM) is an aggressive and currently incurable blood cancer that affects plasma cells made in the bone marrow. Healthy plasma cells make antibodies that help the body fight infection.6 MM is the second most common type of blood cancer, with over 35,000 new cases of MM diagnosed annually in the U.S. and 176,000 globally.7,8 About half of those diagnosed with MM won’t survive beyond five years, and most will receive four or more lines of therapy due to relapse.9 While disease trajectory varies for each person, relapses are nearly inevitable.10 Real-world evidence shows that people with RRMM often become resistant to the three main classes of treatment – proteasome inhibitors, immunomodulatory agents and anti-CD38 monoclonal antibodies – after just a few rounds of therapy, and re-treating with these classes was common.11 The goal of therapy for people with RRMM is to achieve disease control with acceptable toxicity and improved quality of life.12

Prescribing Information for Pfizer Medicines

Please read full Prescribing Information, including BOXED WARNING, for ELREXFIO.

Please read full Prescribing Information for OXBRYTA.

On November 2, 2023 Nuvation Bio Inc. (NYSE: NUVB), a biopharmaceutical company tackling some of the greatest unmet needs in oncology by developing differentiated and novel therapeutic candidates, reported its financial results for the third quarter ended September 30, 2023, and provided a business update (Press release, Nuvation Bio, NOV 2, 2023, View Source [SID1234636834]).

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"We remain focused on strong clinical execution of our NUV-868 program for advanced solid tumors," said David Hung, M.D., Founder, President, and Chief Executive Officer of Nuvation Bio. "We look forward to expanding our clinical pipeline with an IND submission for our first DDC clinical candidate expected before the end of the year, building upon our unwavering commitment to bringing transformative cancer therapies to patients who need them most."

Recent Business Updates

NUV-868, BD2-Selective BETi: Advanced solid tumors

Dosing underway in the Phase 1 monotherapy study and both regimens of the Phase 1b combination study. Nuvation Bio continues to treat patients in the Phase 1 monotherapy study of NUV-868 in advanced solid tumors, the Phase 1b study of NUV-868 in combination with olaparib in patients with ovarian cancer, pancreatic cancer, metastatic castration-resistant prostate cancer (mCRPC), triple negative breast cancer and other solid tumors, and the Phase 1b study of NUV-868 in combination with enzalutamide in patients with mCRPC.
Drug-Drug Conjugate Platform: Solid tumors

Nominated first clinical candidate. Nuvation Bio remains on track to submit an Investigational New Drug (IND) application for an undisclosed DDC candidate with the U.S. Food and Drug Administration by year end 2023.
Third Quarter 2023 Financial Results

As of September 30, 2023, Nuvation Bio had cash, cash equivalents and marketable securities of $619.3 million. For the three months ended September 30, 2023, research and development expenses were $18.6 million, compared to $21.3 million for the three months ended September 30, 2022. The decrease was primarily due to a $0.7 million decrease in personnel-related costs driven by a headcount reduction as well as a $2.0 million decrease in third-party costs related to research services and manufacturing primarily due to the termination of the NUV-422 program.

For the three months ended September 30, 2023, general and administrative expenses were $7.8 million, compared to $8.1 million for the three months ended September 30, 2022. The decrease was primarily due to a $0.6 million decrease in insurance and a $0.1 million decrease in recruiting and computer expenses offset by a $0.4 million increase in personnel-related costs driven by stock-based compensation and other benefits.

For the three months ended September 30, 2023, Nuvation Bio reported a net loss of $19.6 million, or $(0.09) per share. This compares to a net loss of $27.2 million, or $(0.12) per share, for the comparable period in 2022.

On November 2, 2023 Pierre Fabre Laboratories reported that the European Medicines Agency (EMA) validated the submission for BRAFTOVI (encorafenib) + MEKTOVI (binimetinib) for the treatment of adult patients with BRAFV600-mutant advanced non-small cell lung cancer (NSCLC), who are either treatment naïve or have received prior therapy (Press release, Pierre Fabre, NOV 2, 2023, View Source [SID1234636833]).

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The submission is based on the results from the registrational PHAROS study,[1] which by independent review, showed an objective response rate (ORR) of 75% in treatment-naïve patients, with 59% maintaining a response for at least 12 months, and 46% in previously treated patients.[1]

"Lung cancer is the number one cause of cancer death worldwide,[2] and there are currently limited effective targeted treatment options for patients with BRAFV600-mutant advanced NSCLC. With our strategic focus on lung cancer and oncology precision medicine, this submission is the next step in delivering clinically meaningful change to oncology patient populations with high unmet needs," said Eric Ducournau, Chief Executive Officer of Pierre Fabre Laboratories.

The Phase 2 PHAROS trial[1] showed that one 450mg daily dose of BRAFTOVI and two 45mg daily doses of MEKTOVI[1] provided a meaningful clinical benefit for these patients with an ORR of 75% (95% CI: 62, 85) in treatment-naïve patients (n=59), with 59% of them maintaining a response for at least 12 months. For those patients who had received prior therapy (n=39), the ORR was 46% (95% CI: 30, 63), with 33% maintaining a response for at least 12 months. Median progression-free survival (PFS) was not reached at data cut-off for the treatment-naïve group (95% CI: 15.7, NE) and 9.3 months (95% CI: 6.2, NE) for the previously treated group. Median overall survival (OS) was not reached for either subgroup at the time of data cut-off. The most common treatment-related adverse events observed in the PHAROS trial were nausea (50%), diarrhoea (43%), fatigue (32%) and vomiting (29%).

These findings were simultaneously published in the Journal of Clinical Oncology and presented during the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) congress on 4 June 2023.[1]

BRAFTOVI + MEKTOVI are currently approved in Europe for the treatment of adult patients with unresectable or metastatic melanoma with a BRAFV600 mutation.[3],[4] BRAFTOVI in combination with cetuximab is also approved in Europe for the treatment of adult patients with metastatic colorectal cancer (mCRC) with a BRAFV600E mutation who have received prior systemic therapy.[3]

About PHAROS

PHAROS (NCT03915951) is an ongoing, open-label, multicentre, non-randomised Phase 2 study to determine the efficacy and safety of BRAFTOVI + MEKTOVI in 98 patients with BRAFV600E-mutant metastatic NSCLC. Mutations were identified using next-generation sequencing or polymerase chain reaction tests performed at the patient’s local laboratory. The primary endpoint is confirmed ORR per RECIST v1.1, by independent radiology review (IRR); secondary objectives comprise additional efficacy endpoints including DoR, PFS, and OS as well as safety. The trial is being conducted across 56 sites in: Italy, the Netherlands, South Korea, Spain, and the U.S.

The PHAROS trial is sponsored by Pfizer Inc. and conducted with support from Pierre Fabre Laboratories.

About BRAF-mutant advanced Non-Small Cell Lung Cancer (NSCLC)

Lung cancer is the second most common type of cancer and the number one cause of cancer-related death globally.[2] NSCLC accounts for approximately 80-85% of all lung cancers.[5]

Certain lung cancers are driven by acquired genetic abnormalities like a BRAF mutation. By using biomarkers to identify a person’s particular tumour type, treatment can become more personalised and effective, since the molecular makeup of a person’s cancer often determines how they respond to different therapies.

BRAF mutations occur in approximately 3-5% of NSCLC cases.[1] It stimulates tumour cell growth and proliferation by altering the MAP kinase (MAPK) signalling pathway. Targeting components of this pathway could potentially inhibit unchecked tumour growth and proliferation caused by BRAF mutations.[1],[6]

Precision medicine is increasingly being developed for NSCLC patients with genetic changes, such as BRAF mutations, that can be detected using biomarker tests.[7],[8] Advances in targeted therapy and more widespread use of biomarker testing have been associated with significant improvements in population-level NSCLC mortality in recent years.[9]

About BRAFTOVI + MEKTOVI

BRAFTOVI (encorafenib) is an oral small molecule BRAF kinase inhibitor and MEKTOVI (binimetinib) is an oral molecule MEK inhibitor, both of which target key proteins in the MAPK signalling pathway (RAS-RAF-MEK-ERK). Uncontrolled activation of this pathway has been shown to occur in many cancers, including melanoma, CRC, and NSCLC.[1]

In 2018, the European Commission (EC) approved BRAFTOVI + MEKTOVI for adult patients with unresectable or metastatic melanoma with a BRAFV600 mutation. The approval was based on results from the randomised, active-controlled, open-label, multicentre Phase 3 COLUMBUS trial.

In 2020, BRAFTOVI was EC-approved, in combination with cetuximab, for the treatment of adults with metastatic CRC with a BRAFV600E mutation. The approval was based on results from the randomised, active-controlled, open-label, multicentre Phase 3 BEACON CRC trial.

Pfizer has exclusive rights to commercialise BRAFTOVI and MEKTOVI in the U.S., Canada, and all countries in the Latin American, African, and Middle Eastern regions. Ono Pharmaceutical Co., Ltd. has exclusive rights to commercialise both products in Japan and South Korea, Medison has exclusive rights in Israel, and Pierre Fabre Laboratories has exclusive rights in all other countries, including Europe and Asia-Pacific.

The full product and safety information for the use of BRAFTOVI and MEKTOVI are outlined in the Summary of Product Characteristics (SmPC), published in the European public assessment report (EPAR) and available in all official EU languages. The full SmPC can be accessed at: View Source

On November 2, 2023 HotSpot Therapeutics, Inc., a biotechnology company pioneering the discovery and development of oral, small molecule allosteric therapies targeting regulatory sites on proteins referred to as "natural hotspots," reported that it will present preclinical data from the Company’s highly differentiated mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) program in an oral presentation at the 2023 American Society of Hemotology (ASH) (Free ASH Whitepaper) Annual Meeting, taking place December 9-12, 2023, in San Diego, CA (Press release, HotSpot Therapeutics, NOV 2, 2023, View Source [SID1234636832]).

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MALT1 is a component of the CARD11-BCL10-MALT1 (CBM) protein complex, which serves as a key regulator of NFkB signaling in cells, including B and T cells. MALT1 is implicated in a range of hematological malignancies, including Non-Hodgkin’s lymphoma, as well as other lymphomas and selected solid tumors. Leveraging our proprietary Smart Allostery platform, HotSpot has developed first-in-class small molecules designed to selectively inhibit the scaffolding function of MALT1, a dominant driver of the NFkB pathway. This oral presentation will describe the differentiated preclinical profile for HotSpot’s scaffolding inhibitor, including the potential for an improved efficacy and safety profile versus traditional MALT1 inhibitors that target protease function. HotSpot plans to file an IND for HST-1021, its Development Candidate, in 2024.

Presentation details are as follows:

Title: Discovery of Novel, First-in-Class Allosteric Modulators of MALT1 Scaffolding Function with Differentiated Pharmacology for NFκB-Driven Malignancies
Session Name: 605. Molecular Pharmacology and Drug Resistance: Lymphoid Neoplasms: Novel Therapeutic Approaches in Lymphoma and Multiple Myeloma
Session Date and Time: Sat., Dec., 9, 2023, 9:30-11:00 AM PT
Presentation Time: 10:15 AM PT
Location: Manchester Grand Hyatt San Diego, Grand Hall D
Publication Number: 52

On November 2, 2023 Precision Biologics, a clinical stage therapeutics company whose proprietary platform has produced highly targeted monoclonal antibodies, reported that it will deliver a poster presentation on preliminary results of the ongoing phase 2 trial, combining NEO-201 with pembrolizumab for the treatment of patients resistant to prior checkpoint inhibitor therapy at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 38th Annual Meeting at the San Diego Convention Center in San Diego, CA on November 3rd, 2023 (Press release, Precision Biologics, NOV 2, 2023, View Source [SID1234636831]).

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Poster title: Post-treatment neutrophil-to-lymphocyte ratio and gMDSCs as independent prognostic factors for treatment efficacy with monoclonal antibody NEO-201 and pembrolizumab. Click here for a link to the poster.

NEO-201 specifically binds to and kills cells expressing the truncated Core-1 O-glycan. Truncated Core-1 O-glycan expression is found in solid tumors and certain blood cancers. Additionally, NEO-201 binds to and mediates the killing of immune suppressor cells, including regulatory T cells (Tregs) and granulocytic myeloid-derived suppressor cells (gMDSCs), which are thought to diminish the efficacy of cancer immunotherapy.

Infiltration of the tumor microenvironment (TME) by gMDSCs and Tregs is one of the reasons for the development of resistance to checkpoint inhibitors. Depletion of circulating gMDSCs and Tregs may prevent their accumulation in the TME and reverse the tumor resistance to checkpoint inhibitors.

This study demonstrates that NEO-201 binds to gMDSCs in PBMCs from cancer patients. This poster also reports that following treatment, heavily pre-treated patients with durable stable disease showed a reduction of circulating gMDSCs compared to baseline levels. Additional data from the ongoing Phase 2 trial was recently presented at CRI-ENCI-AACR 7th International Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper) Sept 22, 2023, Milan, Italy. This data demonstrated that NEO-201 reduces the quantity of regulatory T cells in PBMCs of cancer patients and this reduction is associated with stabilization of disease. Click Here for a link to the poster from the CRI-ENCI-AACR meeting.

This Phase 2 study is currently enrolling patients with metastatic Non-Small Cell Lung Cancer (NSCLC), Head and Neck Cancers, Endometrial Cancer and Cervical Cancer, who have already progressed on prior checkpoint inhibitor therapy (including prior Keytruda) at the National Cancer Institute, part of the National Institutes of Health, Bethesda, MD. (View Source)

Precision Biologics’ poster will be presented in person at the San Diego Convention Center, San Diego, CA, on Friday November 3rd, 2023. Please stop by poster # 879 for further details at Lunch (12–1:30 p.m.) and Poster Reception (5:10–6:40 p.m.).