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.).

On November 2, 2023 Intensity Therapeutics, Inc. (Nasdaq: INTS), a clinical-stage biotechnology company focused on the discovery and development of proprietary, novel immune-based intratumoral cancer therapies designed to kill tumors and increase immune system recognition of cancers, reported that safety, tolerability and efficacy data from IT-01, the company’s ongoing Phase 1/2 clinical trial of INT230-6, either as a monotherapy or in combination with ipilimumab in patients with relapsed, refractory and metastatic sarcomas, was presented at the Connective Tissue Oncology Society 2023 Annual Meeting being held in Dublin, Ireland from November 1-4, 2023 (Press release, Intensity Therapeutics, NOV 2, 2023, View Source [SID1234636830]). The poster will be displayed for the duration of the Annual Meeting.

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Abstract Title: INTRATUMORAL INT230-6 (CISPLATIN, VINBLASTINE, SHAO) ALONE OR WITH IPILIMUMAB PROLONGED SURVIVAL WITH FAVORABLE SAFETY AND IMMUNE ACTIVATION IN ADULTS WITH REFRACTORY SARCOMAS (NCT 03058289)
Presenter: Christian F. Meyer, M.D., Ph.D., M.S., Johns Hopkins Sydney Kimmel Cancer Center
Abstract Number: 1574238

Copies of the presentation materials are available on Intensity’s website on the publications, papers and posters page.

Christian Frederick Meyer, M.D., Ph.D., M.S., is an Assistant Professor of Oncology at the Sidney Kimmel Cancer Center at Johns Hopkins University. Dr. Meyer is an investigator for Intensity’s Phase 1/2 clinical trial of INT230-6 and the presenter of the data at CTOS. Dr. Meyer has placed a number of his sarcoma patients into the study due to the demonstrated significant survival prolongation effects of INT230-6.

"The data presented at CTOS highlights the true potential of INT230-6 as both a monotherapy or in combination with ipilimumab. INT230-6 showed an extensive increase in overall survival in metastatic patients over expected results for the heavily pretreated and diverse sarcoma population with an increase of nearly 15 months compared to a synthetic control. Approval of INT230-6, a locally delivered therapy, could be a paradigm-changing treatment for metastatic cancers," said Lewis H. Bender, President and Chief Executive Officer of Intensity. "INT230-6 can fully saturate a tumor with cytotoxic agents to begin apoptosis and cause necrosis when delivered intratumorally, resulting in immune activation consisting of dendritic and T-cell influx to the tumor all while maintaining a favorable safety profile. We have begun the preparations for a Phase 3 study of INT230-6 as a monotherapy and look forward to providing updates on the trial in the future."

IT-01, now complete, was an open-label Phase 1/2 study of INT230-6 in adults with locally advanced, unresectable or metastatic solid tumors, including sarcoma. INT230-6 dose was determined by a target injected tumor’s diameter or volume and administered intratumorally once every two weeks for up to 5 doses with regular maintenance treatment either alone or in combination with ipilimumab at 3 mg/kg every three weeks for 4 doses. The primary endpoint was safety and approximately 90% of subjects had low grade adverse events.

Efficacy Data:

When compared to synthetic controls, INT230-6 alone extended survival in refractory soft tissue sarcoma subjects by approximately 14.9 months. Dosing higher amounts of INT230-6 relative to a patient’s presenting total tumor burden showed increased survival when compared to the synthetic control. An INT230-6 dose relative to the presenting tumor burden of ≥ 40% further improved overall survival and the addition of ipilimumab may improve survival further.

Median overall survival of INT230-6 was ~14.9 months longer than a synthetic control that was developed to predict survival of the enrolled sarcoma population.
Median survival of synthetic control was about 6.8 months.
The INT230-6 Disease Control Rate was 93% in subjects who received at least one dose of INT230-6 as monotherapy.
Safety Data:

Data to date indicate that INT230-6 has a favorable safety profile and is well tolerated.

The majority of treatment-emergent adverse events (TEAEs) were grade 1 or 2 primarily localized pain, fatigue, and nausea.
Two monotherapy and one combination subject experienced a grade 3 adverse event (AE)
There were no reported grade 4 or 5 AEs.
About INT230-6

INT230-6, Intensity’s lead proprietary investigational product candidate, is designed for direct intratumoral injection. INT230-6 was discovered using Intensity’s proprietary DfuseRx℠ technology platform. The drug is composed of two proven, potent anti-cancer agents, cisplatin and vinblastine, and a penetration enhancer molecule (SHAO) that helps disperse potent cytotoxic drugs throughout tumors for diffusion into cancer cells. These agents remain in the tumor resulting in a favorable safety profile. In addition to local disease control, direct killing of the tumor by INT230-6 releases a bolus of neoantigens specific to the patient’s malignancy, leading to engagement of the immune system and systemic anti-tumor effects. Importantly, these effects are mediated without the immunosuppression of concomitant systemic chemotherapy.