On November 7, 2023 BPGbio, Inc., a leading biology-first AI-powered biopharma that focuses on oncology, neurology, and rare diseases, reported plans to present on their groundbreaking AI-developed therapeutics portfolio at the upcoming INV€$TIVAL Showcase in partnership with Jefferies, being held on November 13, 2023 in London, United Kingdom (Press release, BPGbio, NOV 7, 2023, View Source [SID1234637203]).

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"We’re thrilled to present the progress of our AI-developed late-stage clinical assets to investors, industry peers and partners as we continue to advance our pipeline"

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BPGbio will present as part of the event’s Biotech Late Growth Stage track. BPGbio’s President and CEO, Niven R. Narain, PhD, and Executive Chairman Daniel Elliott will detail the company’s progress in advancing BPM31510, their lead drug candidate currently in Phase 2b and Phase 2a trials for Glioblastoma Multiforme (GBM) and Pancreatic Cancer, respectively. Last month, an independent medical advisory board recommended advancement into phase 2b trials for pancreatic cancer. BPM31510 for pancreatic cancer has received orphan drug designation from the U.S. Food and Drug Administration. BPM31510 acts by targeting the mitochondrial machinery and tumor microenvironment (TME) to create a metabolic shift in cancer cells, leading to cancer cell death.

"We’re thrilled to present the progress of our AI-developed late-stage clinical assets to investors, industry peers and partners as we continue to advance our pipeline," said Dr. Narain. "The success of our lead candidate, BPM31510, in clinical trials underscores our biology-first approach to AI drug discovery, which guided our development team throughout the process and optimized our clinical trials with the appropriate patient cohort. We eagerly anticipate advancing these trials, building on our early successes, and applying this approach to other aggressive cancers and diseases with significant unmet medical needs."

The executives will also provide insights into the company’s growing portfolio of therapeutic targets and candidates, including several that are in late-stage clinical trials, which have been identified through BPGbio’s proprietary AI-powered NAi Interrogative Biology Platform. This platform identifies targets, biomarkers, and drugs and assists the development team through both the developmental and clinical trial stages. NAi is now commercially available to pharma, academic and government organizations. The NAi Platform consists of an industry leading 100,000 sample, clinically annotated biobank, with purpose-built Bayesian AI. The platform uses the world’s current fastest supercomputer, Frontier, at Oak Ridge National Laboratory (ORNL), making it the only fully integrated high-performance computing (HPC) platform in the biopharmaceutical industry for AI-driven target nomination, discovery, and molecule design.

BPGbio’s therapeutic pipeline also includes drug candidates for epidermolysis bullosa (EB, orphan drug), squamous cell carcinoma (SCC, orphan drug), sarcopenia, solid and liquid tumors, Huntington’s disease (orphan drug) and Parkinson’s disease.

The company’s diagnostic pipeline includes its prostate diagnostic test pstateDx, as well as tests being developed and validated for the detection of Parkinson’s disease (ParkinsonDx), pancreatic cancer (PancDx), breast cancer, and liver disease.

For more information on the conference, visit: View Source

On November 7, 2023 Nutcracker Therapeutics, Inc., a biotechnology company dedicated to developing transformative RNA therapies through its proprietary technology platform, reported preclinical data for two of its therapeutic candidates: its latest therapeutic candidate, NTX-471, which targets CD47; and the company’s lead mRNA candidate targeting human papillomavirus (HPV)-driven tumors, NTX-250 (Press release, Nutcracker Therapeutics, NOV 7, 2023, View Source [SID1234637202]). These data were presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC’s) 38th Annual Meeting.

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CD47 molecules are transmembrane glycoproteins that signal macrophages not to eat the cells on which they are expressed by binding to signal regulatory protein alpha (SIRPa). Anemia is the most common adverse effect of CD47-targeting molecules, since red blood cells also express CD47. NTX-471 is being developed to specifically target CD47 on cancerous cells with unique mRNA-encoded compositions.

Nutcracker’s scientists engineered bivalent, tetravalent, hexavalent, and octavalent RNA-encoded SIRPa proteins and bispecific SIRPa-antiCCR4 molecules. The performance of these molecules were then assessed in vivo and in vitro. Key highlights of the data include:

The octavalent variant’s cytotoxic activity was similar to that of anti-CD47 molecules currently in clinical trials. But, most importantly, the Nutcracker molecules showed little-to-no binding to red blood cells in vitro
Administering mice with formulated mRNA molecules encoding the tetravalent, octavalent, and bispecific SIRPa fully eradicated established subcutaneous tumors, and resulted in robust protein expression (~10-100ug/ml) with high purity/homogeneity similar to, or better than, DNA-expressed proteins
"We’re excited to share our first set of data on NTX-471 with the scientific community," said Executive Vice President of Research and Early Development Samuel Deutsch, Ph.D. "It’s no secret that anti-CD47 therapeutics have recently hit many roadblocks, and have often struggled to address anemic side effects in patients. Using our proprietary platform and the Nutcracker Manufacturing Unit, our team was able to design and quickly produce multiple RNA molecules to assess in vivo. Through our continued work, we are hopeful that NTX-471 will prove to be a viable solution in using CD47 to eradicate tumor cells, while leaving red blood cells untouched."

Further, Nutcracker presented data on a murine version of its lead candidate, NTX-250, labelled mNTX-250. The lead indication for NTX-250 is cervical intraepithelial neoplasia CIN, a precancerous condition caused by HPV infection, which can progress to cervical cancer if left untreated. HPV-16 is the most prevalent high-risk HPV strain.

Nutcracker compared the activity of mNTX-250 to NTX-010. NTX-010 contains IL-12 and LIGHT components found in NTX-250, but lacks HPV antigens (the components of NTX-250 are detailed in previous communications). Key highlights of the data include:

Two doses of mNTX-250 treatment eradicated well-established HPV16-transformed tumors, and improved overall survival in mice. The treated animals also generated significant numbers of HPV-16 E7 antigen-specific T cells
All treated mice with eradicated tumors showed complete rejection when rechallenged
Mice treated with NTX-010 generated fewer HPV16 antigen-specific T cells. When rechallenged, 6 out of 11 NTX-010-treated mice showed tumor growth
"We developed our platform, including the Nutcracker Manufacturing Unit, specifically to fast track early R&D work for RNA therapies, and to efficiently produce them once ready for patients," said Chief Executive Officer Igor Khandros, Ph.D. "The data we presented at SITC (Free SITC Whitepaper) are a testament to the power of RNA, but also what a solution designed specifically for this modality can enable for drug developers. For example, with NTX-471, delivering mRNA, which encodes anti-CD47 proteins, offers a more straightforward method versus producing the complex proteins using a traditional cell line paradigm. Moreover, modifying the RNA sequence of the prospective anti-CD47 molecule is far more efficient than engineering the final protein product. Our platform has made it possible for Nutcracker to lay a strong and early foundation for our future therapeutic work."

On November 7, 2023 ENB Therapeutics, Inc., a clinical-stage biopharmaceutical company focused on oncology and immunology, reported top-line results from the dual combination arm of the Phase 1b ENBOLDEN-101 study, evaluating ENB-003 in combination with Merck’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) in patients with advanced refractory cancers (Press release, ENB Therapeutics, NOV 7, 2023, View Source [SID1234637201]). The results show encouraging objective responses, disease control and extended progression-free survival in patients with platinum resistant/ refractory ovarian cancer (PROC). The poster, entitled, "ENB-003, an ETBR antagonist, in combination with pembrolizumab, shows promise in microsatellite stable platinum refractory/resistant ovarian cancer: Data from the ENBOLDEN-101 Phase 1B study" was presented on November 3, 2023 at a poster session at the SITC (Free SITC Whitepaper) 2023 meeting, was held November 1-5, in San Diego, California, USA.

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The data included 5 patients with metastatic microsatellite stable (MSS) PROC who had disease progression after one or more previous lines of treatment. Study treatment consisted of an initial 7-day run-in period of ENB-003 monotherapy, followed by repeated 3-week cycles of ENB-003 in combination with KEYTRUDA.

The data demonstrated that the treatment regimen was safe and well tolerated. The objective response rate (ORR) and disease control rate (DCR- patients exhibiting a response or stable disease) in MSS PROC was 40% and 80% respectively (N=5), including 2 patients with partial responses showing a 95% and 33% reduction in tumor burden respectively, as well as 4 patients with stable disease; 80% of PROC patients demonstrated shrinkage of target lesions overall. The 8-month progression-free survival rate was 60%. This compares favorably with a historical ~20% progression-free survival data at 6 months for single agent anti-PD1 and an ~8% ORR and an ~22% DCR.

"These data, demonstrate that ENB-003 in combination with KEYTRUDA is safe, with encouraging signs of clinical activity and support the combination’s potential to become an effective immunotherapy regimen for MSS primary PROC – a disease that has responded very poorly to available treatments," stated Sumayah Jamal, MD-Ph.D., President, Chief Scientific Officer, and Co-Founder of ENB Therapeutics. "We are extremely pleased with the top-line results from this ongoing study. We look forward to continuing our collaboration with Merck and anticipate initiating Part 2 of the study next year." For more information on this Phase 1/2a study, see NCT04205227.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

About ENB-003

ENB-003 is a selective endothelin B receptor (ETBR) inhibitor that, in preclinical studies, enhances efficacy of CAR-T and anti-PD-1 in solid tumors across multiple cancer types in preclinical studies. In an ongoing multi-center Phase 1/2 clinical trial, early efficacy signals suggest that ENB-003 overcomes resistance to pembrolizumab in heavily pre-treated drug resistant cancer patients. The Phase 2 portion of the ENB-003 + pembrolizumab combination study is expected to start in the first half of 2024. The trial will enroll MSS primary PROC, as well as MSS pancreatic cancer patients and patients with other advanced solid tumors that have failed standard of care.

On November 7, 2023 BostonGene, a leading provider of AI-driven, molecular and immune profiling solutions, and LegoChem Biosciences, Inc. (LCB), a clinical-stage biopharmaceutical company developing next-generation, antibody-drug conjugates (ADCs), reported a collaboration to support the Phase I/II study of LCB84, a TROP2-directed ADC, in patients with advanced cancers (Press release, BostonGene, NOV 7, 2023, View Source [SID1234637200]). This first-in-human study is being conducted at leading cancer institutions in the US and Canada to evaluate the safety and preliminary efficacy of LCB84, both as a single-agent therapy and in combination with an immune checkpoint inhibitor (anti-PD-1 antibody).

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"BostonGene’s integrated analytic and AI capabilities will provide us with crucial insights towards developing breakthrough cancer treatments."

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"We partnered with BostonGene in order to validate theorized mechanisms of ADC efficacy and uncover novel biomarkers to improve patient selection as LegoChem Biosciences progresses towards further clinical validation of our ADC platform technology, enabling safer and more efficacious therapies for cancer patients," said Director of Drug Development Stephen Slocum, PhD at LegoChem Biosciences. "BostonGene’s integrated analytic and AI capabilities will provide us with crucial insights towards developing breakthrough cancer treatments."

"We are excited to collaborate with LCB to support the development of their novel, TROP2-directed ADC, LCB84, and to address the high unmet need in cancer for improved tumor targeting, safety and efficacy," said Andrew Feinberg, President and CEO at BostonGene.

Added Chief Medical Officer Nathan Fowler, MD, "BostonGene’s proprietary discovery platform merges a deep understanding of the human immune system and cancer biology with unparalleled software expertise and capacity. With a pragmatic, results-oriented team approach, we are driven by the potential for a direct impact on the lives of cancer patients. Our accelerated biomarker discovery algorithms support optimized "matching" of patients with therapies that can effectively target the unique characteristics of their cancer."

BostonGene will serve as the study’s central laboratory and analytic partner for exploratory biomarkers, performing in-depth, multi-omic profiling of patients’ tumor tissue and blood samples, including whole-exome sequencing (WES), whole-transcriptome sequencing (RNAseq) of tumor tissue from matched tumor biopsies on the study, and immunoprofiling to identify hundreds of different cell types from a single blood sample. Leveraging its advanced AI and machine learning platforms, BostonGene will also deliver comprehensive analytics to identify predictive biomarkers and optimize the selection of patients most likely to benefit from treatment.

Each patient’s tumor has a unique molecular "fingerprint" that can be identified with BostonGene’s differentiated analytic and software platforms for comprehensive, real-time, cost-efficient results to support the delivery of highly personalized cancer therapies that give patients the best chance of durable responses.

On November 7, 2023 MAIA Biotechnology, Inc., (NYSE American: MAIA) ("MAIA" or the "Company"), a clinical-stage biopharmaceutical company developing telomere-targeting immunotherapies for cancer, reported financial results for the third quarter ended September 30, 2023 and key operational updates (Press release, MAIA Biotechnology, NOV 7, 2023, View Source [SID1234637199]).

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"Our successful and productive third quarter was punctuated by the outstanding data on our lead asset THIO that we recently revealed, and an accelerating pace of enrollment in our THIO-101 Phase 2 trial," said Vlad Vitoc, M.D., MAIA’s Chairman and Chief Executive Officer. "We are expanding our trial in Europe, and with the FDA’s recent clearance for THIO studies in the U.S. as part of THIO-101, we have reached an essential milestone in the clinical development of THIO. Preliminary efficacy data from the trial is excellent and includes an unprecedented disease control rate (DCR) of 100% in second-line NSCLC treatment, far surpassing the standard of care DCR of 53-64%. We achieved the pre-determined statistical requirements to proceed to the next stage of the trial earlier than expected, and we look forward to sharing our continuing progress in the coming months and into 2024."

Third Quarter Business Highlights and Recent Developments

THIO Program

Announced 100% Disease Control in Second-Line Non-Small Cell Lung Cancer Demonstrating Impressive Positive Preliminary Efficacy Data: 100% preliminary DCR was observed in second-line and 88% in third-line, in highly difficult-to-treat patients who already progressed through previous lines of treatment. DCRs across all dose levels met the pre-determined statistical requirements earlier than expected to proceed to next stage of the THIO-101 Phase 2 trial.

Highly Potent Anticancer Activity in Gliomas: MAIA’s lead asset THIO showed highly potent anticancer activity in models of glioma, an aggressive type of brain tumor that originates from glial cells and is among the most difficult-to-treat cancers. As a monotherapy, THIO demonstrated efficacy in multiple glioma cell lines that had acquired resistance to the current state-of-the-art care temozolomide (TMZ).

THIO as Potential Therapy for Pediatric Brain Cancer: Study data showed THIO’s potent anticancer activity in diffuse intrinsic pontine glioma (DIPG), one of the most aggressive tumors affecting the central nervous system in children. The treatment resulted in noticeably increased tumor sensitivity to immune or ionizing radiation therapies.

Higher Anticancer Potency of Next Generation THIO Conjugates: Positive Investigational New Drug-enabling study data on telomere-targeting agents derived from lipid-modified THIO molecules warrant further in vivo in-depth investigation of THIO-like agents as second generation cancer therapies.

THIO-101 Phase 2 Clinical Trial

U.S. FDA Clearance of THIO IND Application: The U.S. Food and Drug Administration (FDA) cleared an Investigational New Drug (IND) application enabling THIO to be evaluated in the U.S. as part of THIO-101, the Company’s ongoing global phase 2 clinical study in patients with advanced non-small cell lung cancer (NSCLC). THIO is being tested in sequential combination with a checkpoint inhibitor (CPI) to evaluate anti-tumor activity and immune response in NSCLC patients.

Strong Pace of Enrollment in THIO-101: 49 patients have been dosed to date at a pace of enrollment that is currently exceeding the average enrollment pace in similar NSCLC trials. Out of the 49 patients dosed, 37 have already completed at least one post baseline assessment.

Continuing Positive Preliminary Survival Data: The first 2 subjects dosed on trial (both receiving 3rd line of treatment) reported long term survival of 14.6 and 12.5 months, respectively, at the latest post baseline assessment with no new anti-cancer treatment initiated. Follow up was ongoing for the first subject at the time of data cut-off.

Third Quarter 2023 Financial Results

Cash Position: Cash totaled approximately $6.1 million as of September 30, 2023, compared to $10.9 million in cash as of December 31, 2022.

Research and Development (R&D) Expenses: R&D expenses were approximately $2.6 million for the quarter ended September 30, 2023, compared to approximately $2.3 million for quarter ended September 30, 2022. The increase was primarily related to an increase in scientific research expenses.

General and Administrative (G&A) Expenses: G&A expenses were approximately $2.4 million for the quarter ended September 30, 2023, compared to approximately $1.7 million for the quarter ended September 30, 2022. The increase for the quarter was primarily related to an increase in professional fees related to the write-off of deferred offering costs and an increase in investor relations costs.

Other Income, Net: Other income was approximately $0.08 million for the quarter ended September 30, 2023, compared to other income, net of $0.19 million for the quarter ended September 30, 2022, primarily related to a change in the fair value of warrant liability.

Net Loss: Net loss was approximately $4.9 million, or $0.36 per share, for the quarter ended September 30, 2023, as compared to net loss of approximately $4.9 million, or $0.48 per share, for the quarter ended September 30, 2022. Weighted average shares outstanding were 13,675,802 in the third quarter of 2023, compared to 10,165,622 in the third quarter of 2022.

For additional information on the Company’s financial results for the quarter ended September 30, 2023, please refer to the Form 10-Q filed with the SEC.

About THIO

THIO (6-thio-dG or 6-thio-2’-deoxyguanosine) is a first-in-class investigational telomere-targeting agent currently in clinical development to evaluate its activity in Non-Small Cell Lung Cancer (NSCLC). Telomeres, along with the enzyme telomerase, play a fundamental role in the survival of cancer cells and their resistance to current therapies. The modified nucleotide 6-thio-2’-deoxyguanosine (THIO) induces telomerase-dependent telomeric DNA modification, DNA damage responses, and selective cancer cell death. THIO-damaged telomeric fragments accumulate in cytosolic micronuclei and activates both innate (cGAS/STING) and adaptive (T-cell) immune responses. The sequential treatment with THIO followed by PD-(L)1 inhibitors resulted in profound and persistent tumor regression in advanced, in vivo cancer models by induction of cancer type–specific immune memory. THIO is presently developed as a second or later line of treatment for NSCLC for patients that have progressed beyond the standard-of-care regimen of existing checkpoint inhibitors.

About THIO-101, Phase 2 Clinical Trial

THIO-101 is a multicenter, open-label, dose finding Phase 2 clinical trial. It is the first trial designed to evaluate THIO’s anti-tumor activity when followed by PD-(L)1 inhibition. The trial is testing the hypothesis that low doses of THIO administered prior to an anti-PD-1 agent will enhance and prolong immune response in patients with advanced NSCLC who previously did not respond or developed resistance and progressed after first-line treatment regimen containing another checkpoint inhibitor. The trial design has two primary objectives: (1) to evaluate the safety and tolerability of THIO administered as an anticancer compound and a priming immune activator (2) to assess the clinical efficacy of THIO using Overall Response Rate (ORR) as the primary clinical endpoint. For more information on this Phase II trial, please visit ClinicalTrials.gov using the identifier NCT05208944.