On November 9, 2024 Marengo Therapeutics, Inc., a clinical-stage biotechnology company pioneering novel approaches for precision T cell activation, reported encouraging initial Phase 1 clinical data from its lead program, invikafusp alfa (STAR0602), during a late-breaking oral presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 39th Annual Meeting taking place in Houston, Texas (Press release, Marengo Therapeutics, NOV 9, 2024, View Source [SID1234648062]).

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This is the first public disclosure of results from the ongoing STARt-001 Phase 1/2 trial (NCT05592626), evaluating invikafusp alfa as monotherapy in biomarker-enriched (TMB-H, MSI-H/dMMR or virally associated) patients with advanced anti-PD-1 resistant, or refractory solid tumors.

Phase 1 data from STARt-001 trial demonstrate early anti-tumor activity, including initial signals of clinical benefit in heavily pre-treated, anti-PD-1 resistant cancer patients. Invikafusp alfa also showed a manageable safety profile consistent with its novel mechanism of action, further supporting its potential as a treatment option across a range of high tumor mutational burden (TMB-H) cancers or virally associated malignancies.

"Having completed Phase 1 and commenced the Phase 2 dose expansion cohorts of STARt-001, Marengo is thrilled to share initial clinical findings that validate our novel selective dual T cell agonist platform," said Zhen Su, M.D., MBA, Chief Executive Officer of Marengo Therapeutics. "The single agent activity observed in Phase 1, especially in PD-1 resistant cold tumors such as colorectal cancer is a critical milestone, and we look forward to further exploring the potential of STAR0602 to become a next-generation backbone IO therapy across a range of tumor types."

Additional highlights from the Phase 1 findings include:

Sustained and selective in vivo expansion of TCRVβ6/Vβ10 T cells was achieved across all 6 dose levels with up to ~500% peak increase post invikafusp alfa treatment

Disease Control Rate (PR + SD) was reported in 50% of 28 patients from all dose escalation cohorts with 32% of patients experienced tumor shrinkage across six tumor types

At the optimal biological dose range (0.08 mg/kg and 0.12 mg/kg), invikafusp alfa had single agent clinical activity with 63% Disease control rate, 50% of patients experienced tumor shrinkage and 25% ORR reported in TMB-H, anti-PD-1 resistant patients

Safety profile was consistent with the T cell activation/expansion mechanism of action (MOA) without corticosteroid or tocilizumab pretreatment. The most common treatment-related adverse events (TRAEs) were mainly transient grade 1 & 2 CRS during first and second infusion without any grade 4 adverse events (AEs) or immune effector cell-associated neurotoxicity syndrome (ICANS)

Recommended Phase 2 dose (RP2D) of 0.08 mg/kg was selected for Phase 2 dose expansion studies based on safety, PK/PD data and preliminary anti-tumor activity
"The first-in-human data suggest that this novel approach to selectively activate and expand Vβ T cell subsets may hold promise for treating patients with advanced solid tumors," said Dr. James L. Gulley, Co-Director of the Center for Immuno-Oncology and Clinical Director of the National Cancer Institute. "The observed unique Vβ T cell biology in humans and selective expansion of Vβ6/Vβ10 across a range of solid tumors, combined with the initial anti-tumor activity, particularly in heavily pre-treated anti-PD-1 resistant cancer patients with TMB-H colorectal cancer, are encouraging signs. The differentiated clinical profile supports further investigation of this unique mechanism of action in the next phase of clinical trials for high unmet medical needs in anti-PD-1 resistant tumors."

Taken together, the data presented from the STARt-001 study underscore invikafusp alfa’s potential as a novel therapeutic option for patients with advanced, PD-1-resistant solid tumors. Marengo has initiated the Phase 2 dose expansion and expects to share initial results in 2H 2025.

Late-breaking oral presentation details:

Title: A Phase 1/2 study of Invikafusp alfa (STAR0602), a first-in-class TCR β chain-targeted bispecific antibody, as monotherapy in patients with antigen-rich solid tumors resistant to anti-PD(L)1.
Conference: 39th SITC (Free SITC Whitepaper) Annual Meeting.
Abstract Number: LBA-1470.
Session Title: Late-Breaking Abstract Session 2.
Session Date and Time: Saturday, November 9, 2024, 11:45 AM – 12:15 PM.
Presenter: James L. Gulley, M.D., Ph.D. (National Cancer Institute, Bethesda, Maryland, USA).

On November 9, 2024 Sapience Therapeutics, Inc., a clinical-stage biotechnology company focused on the discovery and development of peptide therapeutics to address oncogenic and immune dysregulation that drive cancer, reported the presentation of clinical and non-clinical results on its lead programs, ST101 and ST316, at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 39th Annual Meeting, being held November 6-10, 2024, in Houston, TX (Press release, Sapience Therapeutics, NOV 9, 2024, View Source [SID1234648063]).

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ST101 is a first-in-class antagonist of C/EBPβ, currently being evaluated in patients with recurrent and newly diagnosed GBM in the Phase 2 portion of a Phase 1-2 clinical study (NCT04478279). ST316 is a first-in-class antagonist of the interaction between β-catenin and its co-activator, BCL9, a complex responsible for driving oncogene expression in multiple cancers where aberrant Wnt/β-catenin pathway signaling is observed and immune-exclusion in the tumor microenvironment. ST316 is being evaluated in colorectal cancer patients in the Phase 2 portion of a Phase 1-2 study (NCT05848739).

Dr. Jim Rotolo, Sapience’s SVP, Research and Translational Sciences, commented, "I am thrilled to have presented new clinical and biomarker data on ST101, which provides further evidence that C/EBPβ is a multi-faceted target for the treatment of newly diagnosed and recurrent GBM. The inclusion of our presentation in SITC (Free SITC Whitepaper)’s press briefing earlier this week, as one of 8 abstracts of the more than 1,500 received, highlights the novelty and importance of the data we are observing in our clinical study. Through our Phase 2 and Window-of-Opportunity studies, ST101 has demonstrated impressive disease control as well as modulation of the tumor immune microenvironment (TIME) from immunosuppressive to immune-active. This TIME shift is highly compelling given the immunosuppressive environment that is known to limit the efficacy of immune-oncology (I/O) agents in the treatment of GBM."

Dr. Rotolo continued, "We also presented initial clinical pharmacodynamic data from our ST316 Phase 1 study, demonstrating that ST316 dramatically depletes immunosuppressive cells from peripheral blood of patients. In non-clinical studies, we were pleased to see that treatment with ST316 and PD-1 checkpoint inhibitors had positive effects on tumor outcomes and immune activation. These results at SITC (Free SITC Whitepaper), coupled with the data we have from the Phase 1 study, provide further validation that ST316 has the potential to improve existing I/O approaches."

ST101 Oral Presentation Highlights Include:

Title: "ST101, an inhibitor of the transcription factor C/EBPβ, promotes an immune-active tumor microenvironment in a window of opportunity (WoO) study of patients with glioblastoma (GBM)"
Abstract #: 991
Session Title: Biotech Breakthroughs – Solid Tumor IO at the Tipping Point
Date/Time: Friday, November 8, 2024, 1:45 pm – 3:20 pm CST
Session Location: George R. Brown Convention Center, Level 3 – Grand Ballroom B
Presenting Author: Jim Rotolo, Ph.D., SVP, Research & Translational Sciences, Sapience Therapeutics

C/EBPβ activity within tumors promotes GBM growth, chemo-resistance, EMT, and invasion.
C/EBPβ activity in immune cells promotes an immuno-suppressive environment.
ST101, a C/EBPβ antagonist, has demonstrated safety and proof-of-concept activity in a Phase 2 clinical study, showing that treatment with ST101 leads to impaired tumor growth and increased immune activity.
ST101 Window-of-Opportunity study in Newly Diagnosed GBM cohort (n=9, with 8 evaluable):
87.5% post-surgery disease control rate (DCR), with one complete response (CR) and six stable diseases (SD) as of the data cutoff date
8/9 patients are alive as of the data cutoff date (11-76 weeks)
7/9 patients remain on study with median treatment duration of 9.5 months, with 3 patients remaining on the study for greater than 17 months
ST101 Window-of-Opportunity study in Recurrent GBM cohort (n=9):
4/9 (44%) patients had disease control, with 2 PRs and 2 SDs
Window-of-Opportunity biomarker results demonstrate:
ST101 uptake past the blood-brain barrier (BBB) and into the tumor
Disruption of target C/EBPβ
Shift in TIME from immunosuppressive to immune-active
These data support the combination of ST101 with checkpoint inhibitors as a potential treatment for patients with GBM.
ST101 Poster:

Title: "ST101, an inhibitor of the transcription factor C/EBPß, promotes an immune-active tumor microenvironment in a window of opportunity (WoO) study of patients with glioblastoma (GBM)"
Abstract #: 991
Session: Poster Hall
Date/Time:

Friday, November 8, 2024: 9:00 am – 7:00 pm CST
Session Location: George R. Brown Convention Center, Level 1 – Exhibit Halls AB

ST316 Poster Presentation Details:

Title: "ST316, a peptide antagonist of β-Catenin, depletes immunosuppressive myeloid cell populations and enhances anti-cancer immune responses in in vivo tumor models and in patients"
Abstract #: 1451
Session: Poster Hall
Date/Time:

Friday, November 8, 2024, 9:00 am – 7:00 pm CST
Session Location: George R. Brown Convention Center, Level 1 – Exhibit Halls AB
Presenting Author: Claudio Scuoppo, Ph.D., Principal Scientist, Sapience Therapeutics

ST316 disrupts β-catenin-driven immune-exclusion, promoting a shift to an immune-active TIME via depletion of immunosuppressive MDSCs and TAMs, resulting in enhanced cytotoxic T cell activity.
In the clinic, ST316 depletes highly immunosuppressive PMN-MDSCs in Phase I patients.
In human PBMCs, ST316 induces a dose-dependent decrease in immunosuppressive M2 macrophages and a concomitant increase in M1 proinflammatory macrophages, resulting in increased T cell activation.
In murine tumor models, ST316 inhibition of tumor growth is accompanied by a reduction in MDSC population and repolarization of TAMs to an M1-like phenotype.
In murine tumor models, anti-tumor activity of anti-PD-1 treatment is significantly enhanced by combination with ST316, an event accompanied by a reduction of M2-TAMs.
These data provide support for the advancement ST316 through the current Phase 2 study and in combination with existing immune-oncology approaches to improve responses.
About ST101
ST101, a first-in-class antagonist of C/EBPβ, has completed the main portion of a Phase 2 dose expansion study in recurrent GBM (rGBM) (NCT04478279). An ongoing window-of-opportunity sub-study is evaluating ST101 as a monotherapy in patients with rGBM and in combination with radiation and temozolomide in patients with newly diagnosed GBM (ndGBM), with patients receiving ST101 before and after surgical resection in both cohorts. ST101 has been granted Fast Track designation for rGBM from the U.S. FDA and orphan designations for glioma from the U.S. FDA and the European Commission.

About ST316
ST316 is a first-in-class peptide antagonist of the interaction between β-catenin and its co-activator, BCL9, a complex responsible for driving oncogene expression in multiple cancers where aberrant Wnt/β-catenin pathway signaling is observed. ST316 is being evaluated in the Phase 2 portion of a Phase 1-2 dose-escalation and expansion study (NCT05848739). The Phase 1 portion completed enrollment in July 2024. In the Phase 2 dose expansion, ST316 is being tested in colorectal cancer patients in combination with relevant standards of care and in multiple lines of treatment. Sapience is conducting the Phase 2 study across several sites in the United States.

On November 8, 2024 Monopar Therapeutics Inc. ("Monopar" or the "Company") (Nasdaq: MNPR), a clinical-stage biotechnology company focused on developing innovative treatments for patients with unmet medical needs, reported third quarter 2024 financial results and summarized recent developments (Press release, Monopar Therapeutics, NOV 8, 2024, View Source [SID1234648031]).

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Recent Developments

ALXN-1840 for Wilson disease – Late Stage

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On October 23, 2024, the Company entered into an exclusive license with Alexion, AstraZeneca Rare Disease whereby the Company gained worldwide rights to develop and commercialize ALXN-1840 (bis-choline tetrathiomolybdate). ALXN-1840 is a drug candidate for Wilson disease that is in late-stage development, having already completed a Phase 3 clinical trial. Monopar will be assembling a regulatory package and initiating discussions with the FDA, with an initial focus on Wilson disease patients with more severe symptoms. More details on this transaction can be found here (link).

MNPR‐-101 for Radiopharmaceutical Use – Phase 1

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In August 2024, the Company received regulatory clearance in Australia to commence a first-in-human Phase 1a therapeutic clinical trial of its novel urokinase plasminogen activator receptor (uPAR)-targeted radiopharmaceutical therapy MNPR-101-Lu (MNPR-101 conjugated to lutetium-177) in patients with advanced solid cancers. The Company activated its first clinical trial site and launched the study in October 2024; the trial is currently active and recruiting patients.

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In September 2024, the Company announced positive early clinical data from its ongoing open-label Phase 1 imaging and dosimetry clinical trial of MNPR-101-Zr that validate the tumor-targeting ability of MNPR-101-Zr. In October, the Company presented additional clinical data at the European Association of Nuclear Medicine Annual Congress 2024. The data demonstrate clear and durable tumor uptake of MNPR-101-Zr in a patient with advanced ovarian cancer and show favorable biodistribution with low off-target binding.

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The Company is also actively exploring opportunities to expand its radiopharmaceutical pipeline primarily through internal development efforts. In October 2024, the Company announced the filing of a provisional patent application for new radiopharmaceutical compounds and a family of linkers used to connect radioisotopes with targeting agents, including its uPAR-targeting antibody MNPR-101. This provisional patent could enable the Company to use these linkers to create new proprietary radiopharmaceuticals to pursue well-established, high-value cancer targets of interest.

Capital Raise

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On October 30, 2024, the Company completed a registered public offering of 1,181,540 shares of the Company’s common stock at $16.25 per share, generating net proceeds of approximately $17.7 million, after deducting placement agent fees and other estimated offering expenses.

Results for the Third Quarter Ended September 30, 2024 Compared to the Third Quarter Ended September 30, 2023

Cash and Net Loss

Cash and cash equivalents as of September 30, 2024, were $6.0 million. As noted above, the Company completed a registered public offering on October 30, 2024 that yielded net proceeds to the Company of approximately $17.7 million, after deducting placement agent fees and other estimated offering expenses.

Monopar projects that its current funds will be sufficient to continue operations at least into the first half of 2026, including to: (1) assemble a regulatory package and initiate discussions with the FDA on ALXN-1840 for Wilson disease; (2) continue to conduct and conclude its first-in-human imaging and dosimetry Phase 1 clinical trial with MNPR-101-Zr; (3) continue to conduct its first-in-human therapeutic radiopharma clinical trial with MNPR-101-Lu; (4) advance its preclinical MNPR-101-Ac program into the clinic, and (5) invest in internal R&D projects to expand its radiopharma pipeline.

Net loss for the third quarter of 2024 was $1.3 million, or $0.37 per share, compared to net loss of $2.0 million, or $0.69 per share, for the third quarter of 2023.

Research and Development (R&D) Expenses

R&D expenses for the three months ended September 30, 2024 were $984,000, compared to $1,317,000 for the three months ended September 30, 2023. This represents a decrease of $333,000 attributed to (1) a decrease in camsirubicin manufacturing costs of $301,000 due to the Company’s decision to wind down that program, and (2) a decrease of $218,000 in Validive clinical trial related expenses due to the closure of the trial in March 2023. These decreases were partially offset by a net increase of $186,000 due to other R&D expenses attributable to MNPR-101 for radiopharmaceutical use.

General and Administrative (G&A) Expenses

G&A expenses for the three months ended September 30, 2024 were $591,000, compared to $749,000 for the three months ended September 30, 2023. This represents a decrease of $158,000 primarily attributed to (1) a reduction of stock based compensation expenses of $146,000 due to the full vesting of the 2020 grants in the fourth quarter of 2023, and (2) a decrease in stock-based compensation to the CEO and the board of directors of $64,000 as no equity awards have been issued to the CEO and the board of directors to date in 2024, partially offset by a net increase in consulting and other G&A expenses of $52,000.

On November 8, 2024 Dizal (SSE:688192), a biopharmaceutical company committed to developing novel medicines for the treatment of cancer and immunological diseases, announced today the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) seeking approval of sunvozertinib for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) exon 20 insertion mutations (exon20ins), as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy (Press release, Dizal Pharma, NOV 8, 2024, View Source [SID1234648047]).

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Previously, sunvozertinib received accelerated approval in China, making it the world’s first and only oral drug for NSCLC patients with EGFR exon20ins. It has also been granted Breakthrough Therapy Designations (BTDs) by both the U.S. FDA and the China Center for Drug Evaluation (CDE) for treating EGFR exon20ins NSCLC.

The submission is supported by results from the WU-KONG1 Part B study, a multinational pivotal study investigating the efficacy and safety of sunvozertinib in relapsed or refractory EGFR exon20ins NSCLC patients from Asia, Europe, North America, and South America. Sunvozertinib met the primary endpoint by demonstrating statistically significant and clinically meaningful objective response rate (ORR), as assessed by an independent review committee (IRC), while maintaining a manageable safety profile. Data from the study were presented in an oral session at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

"We are encouraged by the potential of sunvozertinib as a single oral agent to improve outcomes for patients with EGFR exon20ins NSCLC." said Xiaolin Zhang, PhD, CEO of Dizal. "The filing for approval of sunvozertinib marks Dizal’s first NDA submission to the FDA, which represents an important step forward as we continue our efforts to address unmet medical needs globally. We look forward to working closely with the FDA on their review of our application."

Lung cancer is the leading cause of cancer incidence and mortality worldwide. NSCLC accounts for approximately 80%-85% of all lung cancers. Patients with NSCLC harboring EGFR exon20ins are reported to have poorer prognosis than those with other EGFR sensitizing mutations. Sunvozertinib, with its innovatively designed molecular structure, provides enhanced efficacy, safety, and ease of administration.

About sunvozertinib (DZD9008)

Sunvozertinib is an irreversible EGFR inhibitor discovered by Dizal scientists targeting a wide spectrum of EGFR mutations with wild-type EGFR selectivity. In August 2023, sunvozertinib received approval from NMPA to treat advanced NSCLC with EGFR exon20ins after platinum-based chemotherapies. The approval is based on the results of WU-KONG6 study, the pivotal study of sunvozertinib in platinum-based chemotherapy pretreated NSCLC with EGFR exon20ins. The primary endpoint of the study was the confirmed overall response rate (cORR) as assessed by the Independent Review Committee (IRC) reached 60.8%. Anti-tumor efficacy was observed across a broad range of EGFR exon20ins subtypes, and in patients with pretreated and stable brain metastasis. In addition, sunvozertinib also demonstrated encouraging anti-tumor activity in NSCLC patients with EGFR sensitizing, T790M, and uncommon mutations (such as G719X, L861Q, etc.), as well as HER2 exon20ins.

Sunvozertinib showed a well-tolerated and manageable safety profile in the clinic. The most common drug-related TEAEs (treatment-emergent adverse event) were Grade 1/2 in nature and clinically manageable.

Two global pivotal studies are ongoing in ≥ 2nd line (WU-KONG1 Part B) and 1st line setting (WU-KONG28), respectively, in NSCLC patients with EGFR exon20ins.

Pre-clinical and clinical results of sunvozertinib were published in peer-reviewed journals Cancer Discovery and The Lancet Respiratory Medicine.

On November 8, 2024 NanoCell Therapeutics, Inc. ("NanoCell"), a company developing a non-viral, DNA-based in vivo gene therapy platform, reported animal proof of concept data from its lead program utilizing targeted lipid nanoparticle (tLNP) technology for in vivo CAR-T cell generation (Press release, NanoCell Therapeutics, NOV 8, 2024, View Source [SID1234648032]).

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"The studies demonstrated successful targeting and stable CAR expression in a human PBMC engrafted mouse model evaluating the company’s tLNP technology. These findings were initially shared at the 31st Annual Congress of the European Society of Gene & Cell Therapy (ESGCT) in Rome last month. Additional data are being presented at the SITC (Free SITC Whitepaper) 39th Annual Meeting in Houston (Abstract #284)]"

These preclinical data demonstrate the potential of our cell-directed, lipid-enabled delivery platform," said Maurits Geerlings, CEO of NanoCell. "As we progress from platform validation, we are advancing our lead clinical construct, a dual-CAR CD19/CD22 targeting B cell malignancies and autoimmune diseases."

"Our proof of concept studies demonstrate that our cell-directed, lipid-enabled delivery system can achieve stable CAR expression in T cells in vivo," said Dr. Jacek Lubelski, Chief Technology Officer of NanoCell. "These results prove the mechanism of action for our non-viral vector technology approach."

Click here to view Abstract #284

To learn more about our work and stay updated about our latest developments, please visit our website at View Source