On September 12, 2024 Monopar Therapeutics Inc. (Nasdaq: MNPR), a clinical-stage radiopharma company focused on developing innovative treatments for cancer patients, reported positive early data from its ongoing open-label MNPR-101-Zr Phase 1 imaging and dosimetry clinical trial confirming MNPR-101-Zr’s tumor targeting ability in humans (Press release, Monopar Therapeutics, SEP 12, 2024, View Source [SID1234646534]).

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MNPR-101 is Monopar’s proprietary first-in-class humanized monoclonal antibody that targets cancers expressing the urokinase plasminogen activator receptor (uPAR). These include a majority of all triple-negative breast, colorectal, bladder, ovarian, gastric, and pancreatic cancers.

A total-body positron emission tomography (PET) image was taken at 168 hours (7 days) post administration of MNPR-101-Zr (a zirconium-89 imaging radioisotope conjugated to MNPR-101) of the first cancer patient in the trial with one of the known high uPAR-expressing cancer types. The results, seen in Figure 1, demonstrate the specificity, durability, and uptake of MNPR-101-Zr in the metastatic tumors relative to normal tissue. The regions of higher uptake also align with the locations of the previously observed metastatic tumors on conventional FDG PET imaging.

"This is exactly what we had hoped to see – highly preferential uptake in the tumor," said Andrew Cittadine, Monopar’s Chief Operating Officer.

MNPR-101-Zr was evaluated against FDG, the gold standard for detecting metastatic tumors.

Figure 2 shows FDG uptake in its highest-uptake tumor compared to MNPR-101-Zr uptake in the same tumor imaged on the same Siemens Biograph Vision Quadra PET/CT scanner.

"At the Melbourne Theranostic Innovation Centre, we utilize one of the world’s most sensitive PET/CT scanners. Using the same scanner for FDG and MNPR-101-Zr, the results show MNPR-101-Zr achieved uptake at sites of known disease with retention out to late points, which is promising for future therapeutic translation," said Professor Rodney Hicks, MBBS(Hons), MD, FRACP, FICIS, FAAHMS, lead investigator on the MNPR-101-Zr Phase 1 imaging and dosimetry clinical trial.

Monopar recently received clearance in Australia to initiate an MNPR-101-Lu Phase 1 therapeutic clinical trial [link] which is currently scheduled to launch in the fourth quarter of this calendar year.

"We are looking forward to sharing additional data at the upcoming European Association of Nuclear Medicine 2024 Annual Congress to be held in Hamburg, Germany on October 19-23, 2024, where our abstract has been accepted as a ‘Top-Rated Oral Presentation’ within the Scientific Program," said Chandler Robinson, MD, Monopar’s Chief Executive Officer.

Further information about the ongoing MNPR-101-Zr Phase 1 imaging and dosimetry clinical trial is available at www.ClinicalTrials.gov under study identifier NCT06337084.

On September 12, 2024 BPGbio, Inc., a leading biology-first, AI-powered, clinical stage biopharma focused on mitochondrial biology and protein homeostasis, reported that researchers will present two posters on the ongoing phase 2 trial (NCT04752813) of BPGbio lead candidate, BPM31510, in patients with newly diagnosed glioblastoma multiforme (GBM) at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2024, taking place September 13-17 in Barcelona (Press release, BPGbio, SEP 12, 2024, View Source [SID1234646551]).

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Seema Nagpal, MD, Clinical Professor of Neurology at Stanford Medicine and principal investigator of the trial, will be presenting the latest data from the ongoing trial which has enrolled sixteen (16) patients and seven (7) completed the study. Dr. Nagpal and her colleagues at Stanford will also present the cutting-edge quinomics assessment of BPM31510 which shows visualized in vivo effect of the drug on an experimental glioma model and in the brain and provides data validating metabolic activity.

"We are excited to present the latest data from the BPM31510 GBM phase 2 trial at the ESMO (Free ESMO Whitepaper) Congress," said Dr. Seema Nagpal, Clinical Professor of Neurology at Stanford Medicine and principal investigator of the trial. "GBM remains one of the most aggressive and lethal forms of brain cancer and the new data obtained from our clinical research have provided significant insights into its treatment."

"Being able to visually see exactly how a drug is working metabolically on an aggressive experimental brain tumor and in the brain uncovered new findings related to brain cancer therapeutic development," said Lawrence Recht, MD, Professor of Neurology and of Neurosurgery at Stanford Medicine. "We look forward to sharing this exciting data with industry peers and fellow researchers."

BPM31510, combined with Vitamin K and standard chemoradiation, is being tested in a single-arm Phase 2b trial across four U.S. sites, with a total target enrollment of 50 patients.

"The preliminary results from the ongoing clinical trial support our biology-first, AI-driven approach, optimizing patient selection and streamlining drug development," said Niven R. Narain, Ph.D., President and CEO of BPGbio, Inc. "We are eager to continue work with the Stanford team and to collaborate with researchers at other top medical centers to complete enrollment in the trial."

Poster Presentation Details:

Title: Trial in Progress (TiP): A Phase 2 Study of BPM31510 (a lipid nanodispersion of oxidized CoQ10) with Vitamin K in combination with Standard of Care (SOC) RT and TMZ in Glioblastoma Multiforme (GBM) patients without prior therapy

Date and Time: Monday, September 16, 2024, 9:00-17:00 CEST

Presentation Number: 499TiP

Speaker: Dr. Seema Nagpal

Title: Comprehensive Quinomics Assessment of BPM31510IV Treatment in Advanced Glioblastoma Multiforme Patients

Date and Time: Monday, September 16, 2024, 9:00-17:00 CEST

Presentation Number: 472P

Speaker: Dr. Seema Nagpal

These posters will be available on BPGbio.com following the ESMO (Free ESMO Whitepaper) meeting.

About BPM31510

BPM31510 is BPGbio’s lead candidate in late-stage development for glioblastoma multiforme (GBM) and pancreatic cancer. The compound has demonstrated a tolerable safety profile and shown potential clinical benefit in both populations. The mechanism of action of BPM31510 was first validated by data from BPGbio’s NAi Interrogative Biology platform, which suggested that there is a hallmark shift in the tumor microenvironment (TME) induced by BPM31510 which modulates mitochondrial oxidative phosphorylation in highly aggressive tumors. BPM31510 has been granted Orphan Drug Designation by the FDA for both GBM and pancreatic cancer indications.

On September 12, 2024 NH TherAguix (NHT), a phase II clinical-stage biotechnology company specializing in the development of novel nanomedicine solutions for precision radiotherapy in oncology, reported the completion of enrollment in NANO-GBM phase Ib/II trial, evaluating the combination of AGuIX nanoparticles with radiotherapy and temozolomide in the treatment of newly diagnosed glioblastoma and the publication of the positive Phase Ib outcomes and MRI-based biodistribution data from this trial in the journal Clinical and Translational Radiation Oncology under the title "NANO-GBM trial of AGuIX nanoparticles with radiotherapy and temozolomide in the treatment of newly diagnosed Glioblastoma: Phase Ib outcomes and MRI-based biodistribution" (Press release, NH TherAguix, SEP 12, 2024, View Source [SID1234646535]).

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Glioblastoma progression occurs mainly within the tumor volume after treatment by radiotherapy. To address this challenge, a radiosensitization strategy with intravenous administration of AGuIX nanoparticles is being explored in the NANO-GBM phase Ib/II trial (NCT04881032), which is the firstin-human use of these nanoparticles with radiotherapy and chemotherapy for the treatment of newly diagnosed glioblastoma.

Developed by NH TherAguix, AGuIX is designed to improve tumor targeting and increase radiobiological damage to tumor tissue locally, thanks to its radiation signal amplification capabilities, in the purpose of expanding lifespan of cancer patients

Enrollment completion
Nano-GBM is a multicentric, randomized, open-label and non-comparative Phase Ib/II trial. These patients with unresected or partially resected glioblastoma receive four injections of AGuIX in combination with temozolomide (75 mg/m²/day) and radiotherapy (60 Gy in 30 fractions of 2 Gy), followed by adjuvant temozolomide according to Stupp protocol, as the standard of care.

The aim of the phase IIstudy is to randomize patients within two arms: i) an experimental arm in which patients are treated with AGuIX at a dose of 100 mg/kg in combination with radio chemotherapy (40 patients), and ii) a control arm in which patients are treated with radio chemotherapy alone (20 patients). To date, all patients of the phase II have been successfully enrolled.

The primary endpoint of this phase II study is progression-free survival at 6 months. Secondary endpoints include AGuIX distribution in tumors, progression-free survival, overall survival, overall objective response rate and the safety profile of AGuIX in combination with radiotherapy and temozolomide.

The Phase II final data are expected by mid-2026.
In May 2024, AGuIX has received Fast Track designation from the U.S. Food and Drug Administration (FDA) as a next-generation radio-enhancer for the treatment of malignant gliomas, particularly glioblastoma (GBM). The Company has recently submitted a dossier for a PRIME designation from the European Medical Agency (EMA).

NH TherAguix is also preparing to launch a multicentric, randomized, double-blind pivotal trial in patients with recurrent glioblastoma in 2025.

Publication of the positive Phase Ib outcomes and MRI-based biodistribution
In the Phase Ib part of the NANO-GBM trial, eligible patients were aged 18 to 75 years with newly diagnosed and histologically confirmed glioblastoma with unresected or partially resected glioblastoma. A dose escalation approach was applied to assess 3 dose levels of AGuIX: 50 mg/kg, 75 mg/kg and 100 mg/kg. Patients were treated with radiotherapy (60 Gy), and concomitant and adjuvant temozolomide. Four intravenous injections of AGuIX were delivered during radiotherapy and concomitant temozolomide.

The goal of the phase Ib was to determine the recommended phase II dose (RP2D) by the evaluation of the occurrence of dose-limiting toxicity (DLT), and to evaluate pharmacokinetic and AGuIX biodistribution in glioblastoma on MRI based images.

Eight patients were enrolled and have successfully received four intravenous injections of AGuIX: at 50 mg/kg (1 patient), 75 mg/kg (1 patient), and 100 mg/kg (6 patients). No AGuIX-related DLTs were observed, leading to the determination of the RP2D of AGuIX as 100mg/kg for continuation in the ongoing phase II multicenter randomized trial.

Moreover, the pharmacokinetic data confirmed previous results obtained in the Nanorad study, with AGuIX mean AUC increasing with dose and a mean plasmatic half-life ranging from 0.84 to 1.41 h.

The quantification assessment confirmed the precise and specific biodistribution of AGuIX within the glioblastoma allowing to identify regions with different AGuIX concentration levels, ranging from: moderate (36-123 µM) to high (123-291 µM) and very high (> 291 µM) concentration. These values are in agreement with range of concentration high enough for inducing a radiosensitization effect according to NH TherAguix knowledge and experience.

These results confirm the good safety profile of AGuIX (with no occurrence of severe AGuIX-related toxicity) and the widespread dispersion of nanoparticles throughout glioblastoma. Those outcomes support progression to the multicenter and randomized phase II, utilizing an RP2D of AGuIX of 100mg/kg (4 injections).

On September 12, 2024 Summit Therapeutics Inc. (NASDAQ: SMMT) ("Summit," "we," or the "Company") reported that the Company accepted offers from multiple leading biotech institutional and individual investors to purchase an aggregate of approximately 10.35 million shares of the Company’s common stock at $22.70 per share, the closing price on Wednesday, September 11, 2024, for aggregate gross proceeds to the Company of approximately $235 million. The capital raise was completed without bankers’ fees (Press release, Summit Therapeutics, SEP 12, 2024, View Source [SID1234646552]).

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All of Summit’s Section 16 officers participated in the capital raise. A total of $79 million was raised by insiders, including Robert W. Duggan, Dr. Maky Zanganeh, Manmeet S. Soni, and Bhaskar Anand, as well as Jeff Huber, a member of the Board of Directors, who invested via a controlled entity. The remaining $156 million was raised with multiple leading biopharma institutional investors.

Summit intends to use the net proceeds to advance, in part, the clinical development of ivonescimab, including in non-small cell lung cancer and in settings outside of lung cancer by leveraging the data that will be presented at ESMO (Free ESMO Whitepaper), which may include, but is not limited to, colorectal cancer, and triple-negative breast cancer, in addition to working capital needs and general corporate purposes.

The securities described above have not been registered under the Securities Act of 1933, as amended. Accordingly, these securities may not be offered or sold in the United States, except pursuant to an effective registration statement or an applicable exemption from the registration requirements of the Securities Act. Summit has agreed to file a registration statement with the Securities and Exchange Commission (SEC) registering the resale of the shares of common stock following the closing of the securities purchase agreement.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such jurisdiction.

About Ivonescimab

Ivonescimab, known as SMT112 in Summit’s license territories, the United States, Canada, Europe, Japan, Latin America, including Mexico and all countries in Central America, South America, and the Caribbean, the Middle East, and Africa, and as AK112 in China and Australia, is a novel, potential first-in-class investigational bispecific antibody combining the effects of immunotherapy via a blockade of PD-1 with the anti-angiogenesis effects associated with blocking VEGF into a single molecule. Ivonescimab displays unique cooperative binding to each of its intended targets with multifold higher affinity when in the presence of both PD-1 and VEGF.

This could differentiate ivonescimab as there is potentially higher expression (presence) of both PD-1 and VEGF in tumor tissue and the tumor microenvironment (TME) as compared to normal tissue in the body. Ivonescimab’s tetravalent structure (four binding sites) enables higher avidity (accumulated strength of multiple binding interactions) in the TME with over 18-fold increased binding affinity to PD-1 in the presence of VEGF in vitro, and over 4-times increased binding affinity to VEGF in the presence of PD-1 in vitro (Zhong, et al, SITC (Free SITC Whitepaper), 2023). This tetravalent structure, the intentional novel design of the molecule, and bringing these two targets into a single bispecific antibody with cooperative binding qualities have the potential to direct ivonescimab to the tumor tissue versus healthy tissue. The intent of this design, together with a half-life of 6 to 7 days (Zhong, et al, SITC (Free SITC Whitepaper), 2023), is to improve upon previously established efficacy thresholds, in addition to side effects and safety profiles associated with these targets.

Ivonescimab was engineered by Akeso Inc. (HKEX Code: 9926.HK) and is currently engaged in multiple Phase III clinical trials. Over 1,800 patients have been treated with ivonescimab in clinical studies globally.

Summit has begun its clinical development of ivonescimab in non-small cell lung cancer (NSCLC), commencing enrollment in 2023 in two multi-regional Phase III clinical trials, HARMONi and HARMONi-3, with a plan to initiate HARMONi-7 in early 2025.

HARMONi is a Phase III clinical trial which intends to evaluate ivonescimab combined with chemotherapy compared to placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who have progressed after treatment with a 3rd generation EGFR TKI (e.g., osimertinib).

HARMONi-3 is a Phase III clinical trial which is designed to evaluate ivonescimab combined with chemotherapy compared to pembrolizumab combined with chemotherapy in patients with first-line metastatic squamous NSCLC.

HARMONi-7 is a planned Phase III clinical trial which is intended to evaluate ivonescimab monotherapy compared to pembrolizumab monotherapy in patients with first-line metastatic NSCLC whose tumors have high PD-L1 expression (PD-L1 TPS > 50%).

In addition, Akeso has recently had positive read-outs in two single-region (China), randomized Phase III clinical trials for ivonescimab in NSCLC, HARMONi-A and HARMONi-2.

HARMONi-A was a Phase III clinical trial which evaluated ivonescimab combined with chemotherapy compared to placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who have progressed after treatment with an EGFR TKI.

HARMONi-2 is a Phase III clinical trial evaluating monotherapy ivonescimab against monotherapy pembrolizumab in patients with locally advanced or metastatic NSCLC whose tumors have positive PD-L1 expression (PD-L1 TPS >1%).

Ivonescimab is an investigational therapy that is not approved by any regulatory authority in Summit’s license territories, including the United States and Europe. Ivonescimab was approved for marketing authorization in China in May 2024.

On September 12, 2024 Oncternal Therapeutics, Inc. (Nasdaq: ONCT) (the "Company") reported its decision to discontinue its clinical trials evaluating ONCT-534, its dual action androgen receptor inhibitor for the treatment of patients with metastatic castration resistant cancer, and ONCT-808, its ROR1-targeting autologous CAR T program for the treatment of patients with aggressive B-cell lymphoma, and to explore strategic alternatives (Press release, Oncternal Therapeutics, SEP 12, 2024, View Source [SID1234646537]).

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In the current study, interim Phase 1 results of ONCT-534 did not show clinically meaningful improvements of disease, including prostate-specific antigen (PSA) levels, in the 20 patients treated in eight dosing cohorts with various doses and schedules of administration of ONCT-534. ONCT-534 was generally well tolerated, with dose limiting toxicity observed in 2 of 3 patients at the highest dose tested, 1200 mg given orally once per day.

The results with ONCT-808 at an interim Phase 1 analysis showed anti-tumor activity at every dose tested, including a complete metabolic response lasting eight months and long-term persistence of the CAR-T cells, with expected treatment emergent adverse events for a CAR-T therapy, and one death due to complications of shock at the highest dose tested.

Based on the available clinical data and capital requirements for continued development, the Company has decided to terminate these studies. The Company will focus on exploring strategic alternatives with the goal of maximizing value for its stockholders, which may include asset sales, licensing or other strategic transactions relating to the Company’s development programs or a merger, reverse merger, acquisition, or other business combination involving the Company. While this strategic exploration is ongoing, the Company will discontinue all product development activities and will take other steps to reduce costs, including a reduction in its workforce to preserve cash resources.

"The early results during dose escalation in the Phase 1/2 studies of ONCT-534 in heavily pretreated patients are disappointing, as the study was supported by extensive preclinical data and was designed to address important unmet medical needs for patients with advanced prostate cancer," said James Breitmeyer, M.D., Ph.D., Oncternal’s President and CEO. "In light of these data and the challenging financing environment, we intend to explore strategic options with the hope of advancing and realizing value from our pipeline including ONCT-534, ONCT-808, zilovertamab and ONCT-216."