On November 9, 2022 Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported that its novel inhibitor of the embryonic ectoderm development (EED) protein, APG-5918, has been approved by the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA) to enter a Phase I study in patients with advanced solid tumors or hematologic malignancies (Press release, Ascentage Pharma, NOV 9, 2022, View Source [SID1234623587]). Following the recent clearance for the study in the US, this approval in China marks another milestone for the company’s strategy of simultaneous clinical development in the two countries. APG-5918 is the first domestically developed novel EED inhibitor entering clinical development in China.

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This multicenter, open-label Phase I dose-escalation and dose-expansion study is designed to assess the safety, pharmacokinetics, and efficacy of orally administered APG-5918 in patients with advanced solid tumors or hematologic malignancies. Prof. Ruihua Xu, President and Director of Sun Yat-Sen University Cancer Center, and President of the Chinese Society of Clinical Oncology, will be the principal investigator of this study.

EZH2, which is highly expressed in multiple tumors in humans, was found to promote the development and progression of tumors, and targeted inhibition of EZH2’s methyltransferase activity has already proved to be an effective mechanistic approach for cancer treatment. However, the secondary mutation of EZH2 may lead to acquired drug resistances, while the homologous EZH1 also has methyltransferase (MTase) activity that could limit the effects of EZH2 inhibitors. Studies have shown that the PRC2 complex’s component proteins and EZH2’s histone (MTase; HMTase) activities are highly dependent on the scaffold and modulating effects of EED. Compounds with inhibitory effects on EED, a subunit of PRC2, can disrupt the protein-to-protein interaction between EED and EZH2, culminating in damaged PRC2 functions, H3K27me3-induced silencing of PRC2 expressions, and blockade of the triple-methylation of H3K27.1 Therefore, allosteric targeting of EED has in recent years gained a great deal of traction as a promising approach for inhibiting the replacement of inactivated PRC2.

Discovered and developed by Ascentage Pharma, APG-5918 is an orally active, potent, selective, small-molecule EED inhibitor with high binding affinity. APG-5918 can regulate the epigenetics of tumors and the tumor microenvironment, and therefore has broad therapeutic potential for the treatment of hematologic malignancies, solid tumors, and nononcologic conditions. APG-5918 can selectively bind to the H3K27me3 domain of the EED protein, leading to the conformational changes to H3K27me3’s binding pockets in the EED protein, which can then block EED from interacting with the histone methyltransferase EZH2. Preliminary data showed that APG-5918 has in vitro antiproliferative activity in various tumor cell lines and antitumor activity in patient-derived xenograft (PDX)/cell line-derived xenograft (CDX) models of EZH1-mutant B-cell non-Hodgkin lymphoma, IN1-negative malignant rhabdoid tumor, BAP1-mutant mesothelioma and prostate cancer.

Prof. Ruihua Xu commented, "Targeting PRC2 complex proteins, especially the EED, may be an effective mechanistic approach for treating cancer patients with certain genetic profiles. In both in vitro studies and in vivo studies in animal models, the EED inhibitor APG-5918 has shown clear targeted binding and target-based antitumor activity, thus warranting further clinical evaluations."

Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, said, "This approval of the clinical study of APG-5918 in China came shortly after the clearance for the study in the US, hence signals major progress in Ascentage Pharma’s efforts to simultaneously advance clinical programs in China and the US, and is also a strong testament to our global innovation capabilities. We look forward to closely collaborating with Prof. Xu to advance the clinical development of APG-5918, which we hope will offer a novel therapeutic to patients in need."

Reference

1. Erokhin M, Chetverina O, Győrffy B, Tatarskiy V V, Mogila V, Shtil AA, et al. Clinical correlations of polycomb repressive complex 2 in different tumor types. Cancers 2021;13:3155.

On November 9, 2022 Kinimmune, Inc., a clinical-stage biopharmaceutical company focused on the discovery and development of localized immunotherapies, reported that the company has received $400k in funding from the National Cancer Institute (NCI) at the National Institutes of Health for its Phase I STTR application, "Development of a tumor-retentive immunostimulant as adjunct therapy for solid tumor cancers" (Press release, Kinimmune, NOV 9, 2022, View Source [SID1234623586]). This award will advance the preclinical development of KIN-102, an immunostimulant for intratumoral injection that is designed to turn ‘cold’ tumors ‘hot’ for synergy with immuno-oncology drugs such as checkpoint inhibitors.

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The STTR program at NCI is designed to fuel small businesses on the cutting edge of innovation with nondilutive funding to de-risk and advance promising cancer interventions. STTR grants from the NCI are highly selective and were awarded to just 15% of applicants in 2021. "Winning this award provides invaluable scientific validation in addition to the research funding," shared Cory Berkland, President and Co-founder of Kinimmune.

Kinimmune was founded out of Cory Berkland’s laboratory at the University of Kansas in collaboration with Nabil Alhakamy of King Abdulaziz University. Their work uncovered versatile anti-tumor utilities for glatiramer acetate, a long-approved multiple sclerosis drug. "The field’s understanding of glatiramer acetate’s therapeutic mechanism has evolved throughout its time in the clinic," said Danny Griffin, CSO of Kinimmune. He continued, "through a thorough physicochemical analysis we uncovered that its properties were conducive for retention and immune activation at the site of administration." This work led to the inception of Kinimmune and a Phase I "Window of Opportunity" trial at the University of Kansas Medical Center, where intratumorally injected glatiramer acetate’s safety and effects on the tumor immune profile are being studied (NCT03982212).

KIN-102 is a small volume nanosuspension of glatiramer acetate complexed with the immunostimulant CpG. KIN-102 combines the documented safety of FDA-approved glatiramer acetate with the abundance of late-stage clinical data of CpG in cancer, vaccines, and infectious disease. By conferring glatiramer acetate’s tumor adhesive properties to CpG’s potency, KIN-102 aims to retain this robust TLR9 agonist in solid tumors, thus amplifying anti-tumor immune effects at the site of injection while mitigating safety concerns caused by systemic exposure.

"This award from the NCI will help Kinimmune continue the preclinical development of KIN-102," shared Nabil Alhakamy, COO and Co-Founder of Kinimmune. "In 2021, King Abdulaziz University seeded Kinimmune with a financial investment, and additional resources from the University of Kansas Medical Center and BioGenerator Ventures have gone far to bring us to this point while continuing to catalyze our progress."

About KIN-102

KIN-102 is a tumor-adhesive formulation of the immunostimulant CpG. Designed to persist in tumor tissue, KIN-102 is intended to mitigate systemic immune-related adverse events while potentiating immune activity in the tumor microenvironment and draining lymph nodes. By localizing TLR9 ligation to the tumor microenvironment, KIN-102 is intended to turn ‘cold’ tumors ‘hot.’

On November 9, 2022 Immunome, Inc. (Nasdaq: IMNM), a clinical-stage biopharmaceutical company that utilizes its human memory B cell platform to discover and develop first-in-class antibody therapeutics, reported that it is presenting a poster at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 37th Annual Meeting in Boston, Massachusetts highlighting the Company’s preclinical data of IMM20059, a novel anti-epsin 1(EPN1) antibody (Press release, Immunome, NOV 9, 2022, View Source [SID1234623585]).

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"We continue to be pleased with the robust capabilities of our Discovery Engine to identify novel anti-tumor targets, including those that are abnormally (ectopically) expressed on tumor cells which have the potential to fundamentally shift treatment paradigms," commented Purnanand Sarma, PhD, President and CEO of Immunome. "While further preclinical work will be required, we are quite encouraged by the results presented at SITC (Free SITC Whitepaper) today. Treatment with the IMM20059 + atezolizumab combination resulted in over a 50% reduction in tumor volume (p<0.05) compared to isotype-treated control, greater than either one separately. This leads us to believe that there is a potential combinatorial effect between the two pathways, and we look forward to exploring this phenomena further in additional pre-clinical studies."

Lack of response and immunoresistance to checkpoint inhibitors is a well-known challenge in cancer treatment. While the epsin-1 protein is known to be upregulated in a variety of tumor types, it can also be ectopically expressed on the tumor cell surface, as demonstrated in Immunome’s poster, offering a new approach to cancer therapy. Insights into the role of epsin-1 as a potential target for cancer is evolving, but research by others1 also suggests targeting EPN1 has the potential to inhibt tumor growth. The findings presented by Immunome at SITC (Free SITC Whitepaper) further suggest that combining an EPN1-targeting antibody, like IMM20059, with checkpoint inhibitor treatment could reactivate or increase immune response to the tumor.

Immunome Poster at SITC (Free SITC Whitepaper) Annual Meeting (November 8-12, 2022):

Title: IMM20059, a novel anti-EPN1 antibody, in combination with atezolizumab significantly enhances tumor regression in the B16.F10 syngeneic melanoma model compared to anti-PD-L1 monotherapy
Authors: Fang Shen, PhD, John P. Dowling, Pavel A. Nikitin, Cezary R. Swider, Chris Nicolescu, Halley Shukla, Jamie L. Bingaman-Steele, Nirja B. Patel, Eden L. Sikorski, Benjamin C. Harman, Jillian M. DiMuzio, Karen Lundgren, Yumi Ohtani, Michael J. Morin, Matthew K. Robinson
Link: View Source
Date/Time: Nov. 10, 2022/9:00am
Poster/Abstract Number: 823

The poster presentation, IMM20059, a novel anti-EPN1 antibody, in combination with atezolizumab significantly enhances tumor regression in the B16.F10 syngeneic melanoma model compared to anti-PD-L1 monotherapy, highlights novel discoveries related to combinatorial activity between existing immune checkpoint inhibitors and the novel tumor target epsin 1 (EPN1).

Immunome’s preclinical research of IMM20059 in this poster demonstrated that:

EPN1 is upregulated in multiple cancers and is ectopically expressed on tumor cell surfaces.
IMM20059 binds with high affinity to both purified EPN1 protein and to the surface of B16.F10 melanoma tumor cells.
In the combination treatment of IMM20059 and anti-PD-L1 atezolizumab, significant tumor regression was induced compared to IMM20059 or atezolizumab treatment alone, suggesting a combinatorial effect between the two anti-tumoral pathways.
Combination treatment enhanced the production of intratumoral chemokines, MIP-1a, MIP-1b, and RANTES.
About SITC (Free SITC Whitepaper)

Established in 1984, the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) is a nonprofit organization of medical professionals dedicated to improving cancer patient outcomes by advancing the development, science and application of cancer immunotherapy and tumor immunology. SITC (Free SITC Whitepaper) is comprised of influential basic and translational scientists, practitioners, health care professionals, government leaders and industry professionals around the globe. Through educational initiatives that foster scientific exchange and collaboration among leaders in the field, SITC (Free SITC Whitepaper) aims to one day make the word "cure" a reality for cancer patients everywhere. Learn more about SITC (Free SITC Whitepaper), our educational offerings and other resources at sitcancer.org and follow us on Twitter, LinkedIn, Facebook and YouTube.

On November 9, 2022 MAIA Biotechnology, Inc., (NYSE American: MAIA) ("MAIA", the "Company"), a clinical-stage biopharmaceutical company developing targeted immunotherapies for cancer, reported financial results for the third quarter ended September 30, 2022, and provided a corporate update (Press release, MAIA Biotechnology, NOV 9, 2022, View Source [SID1234623584]).

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"The clinical development of THIO continues to be our primary focus. As we move into the final quarter of the year, we plan to share our safety data from the THIO-101 trial," said Vlad Vitoc, M.D., MAIA’s Chairman and Chief Executive Officer. "We remain focused on advancing our strong clinical pipeline which includes, but is not limited to, completing the IND filing for THIO-101 and disclosing preliminary efficacy data in 2023."

Corporate Highlights

Oral Presentation of Novel THIO Platform: Conducted an oral presentation covering the novel THIO platform at the XIV International Round Table on Nucleosides, Nucleotides, and Nucleic Acids, which took place in Stockholm, Sweden on August 28 – 31, 2022.

Trial Design Presented at ESMO (Free ESMO Whitepaper) 2022: Presented the design of its ongoing THIO-101 trial, a multicenter, open-label, dose-finding Phase 2 trial evaluating THIO sequenced with cemiplimab in patients with advanced Non-Small Cell Lung Cancer, at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2022, held from September 9th to 13th in Paris, France.

Data Presented at the Triple Meeting Symposium: Presented the results of a study of the anticancer agent 6-thio-dG (THIO) in hepatocellular carcinoma (HCC) in vitro and in vivo models at the Triple Meeting (EORTC-NCI-AACR) (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics. The symposium took place on October 26-28, 2022, in Barcelona, Spain.

Longevity Stock Index Listing: MAIA has been added in the Longevity Stock Index, which was created to quantify and clarify the longevity industry. This index is the first of its kind within longevity, which is aimed at quantifying and bringing attention to the rapidly growing human aging market.

Third Quarter 2022 Financial Results

Cash Position: The Company had cash totaling approximately $14.1 million as of September 30, 2022, compared to $10.6 million in cash as of December 31, 2021. Current cash, which included the proceeds from the initial public offering completed in July 2022, is anticipated to be sufficient to fund operations for the next 12 months.

Research and Development (R&D) Expenses: R&D expenses were approximately $2.3 million for the quarter ended September 30, 2022, compared to approximately $1.1 million for the same quarter of 2021. The increase for the quarter was primarily due to the increase in clinical expenses related to clinical preparation and the startup of the THIO trials of approximately $0.7 million, an increase in payroll and bonus expenses of approximately $0.6 million, and an increase of approximately $0.1 in professional fees offset by a decrease in stock-based compensation of approximately $0.1 million. R&D expenses included approximately $0.2 million and $0.3 million of non-cash stock compensation expense in the third quarter 2022 and 2021, respectively.

General and Administrative (G&A) Expenses: G&A expenses were approximately $1.7 million for the quarter ended September 30, 2022, compared to approximately $1.2 million for the same quarter of 2021. The increase for the quarter was primarily due to approximate increases in payroll and bonus expenses of $0.2 million, an increase of approximately $0.5 million of other expenses related to the costs of operating as a public company, offset by decreases in stock-based compensation of approximately $0.1 million and professional fees of approximately $0.1. G&A expenses included approximately $0.3 million and $0.5 million of non-cash stock compensation expense in the quarters ended September 30, 2022, and 2021, respectively.

Other Income (Expense): Other income was approximately $0.1 million for the quarter ended September 30, 2022, and other expense for the quarter ended September 30, 2021 was approximately $3.0 million. Other income in the quarter ended September 30, 2022, consisted primarily of approximately $0.1 million in Australian research and development incentives. Other expense for the quarter ended September 30, 2021, primarily consisted of interest expense of approximately $0.5 million, expense for the change in the fair values of the warrant liability of approximately $0.1 million, expense for the change in the fair value of the bifurcated embedded features of approximately $0.1 million, and the loss on extinguishment of convertible notes of approximately $2.3 million.

Net Income (Loss): Net loss was approximately $3.9 million for the quarter ended September 30, 2022, as compared to net loss of approximately $5.2 million for the same quarter of 2021.

About THIO

THIO (6-thio-dG or 6-thio-2’-deoxyguanosine) is a 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. THIO is being 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.

On November 9, 2022 SQZ Biotechnologies (NYSE: SQZ), focused on unlocking the full potential of cell therapies for multiple therapeutic areas, reported third quarter 2022 financial results and recent portfolio updates (Press release, SQZ Biotech, NOV 9, 2022, View Source [SID1234623583]).

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"I am proud of the SQZ team’s accomplishments this quarter, including our publication showcasing the AAC platform, advancing our autoimmune preclinical work, and progress made developing our integrated point-of-care manufacturing system," said Armon Sharei, Ph.D., CEO and Founder at SQZ Biotechnologies. "As we head into the final stretches of the year, we look forward to sharing the latest available clinical data from our three oncology trials."

Third Quarter 2022 and Recent Portfolio Updates

SQZ Antigen Presenting Cell ("APC") Platform in Oncology

Continued enrollment of high dose monotherapy and combination with checkpoint inhibitors in the Phase 1/2 (SQZ-PBMC-HPV-101) trial
Anticipate additional monotherapy data in the highest-dose cohort and initial, interim data for patients in combination with checkpoint inhibitors
SQZ Enhanced Antigen Presenting Cell ("eAPC") Platform in Oncology

Continued enrollment for the monotherapy stage of the COMMANDER-001 Phase 1/2 (SQZ-eAPC-HPV) trial
Anticipate initial cohort 1 data by the end of 2022
SQZ Activating Antigen Carriers ("AAC") Platform in Oncology

Published comprehensive preclinical research in Frontiers in Immunology
Continued enrollment for the monotherapy stage of the ENVOY-001 Phase 1/2 (SQZ-AAC-HPV-101) trial
SQZ Tolerizing Antigen Carriers ("TAC") Platform in Immune Tolerance

Progressed studies supporting anticipated TAC Investigational New Drug (IND) submission for celiac disease in the first half of 2023
Company’s Point-of-Care (POC) manufacturing system intended to produce clinical batches and be operated outside of an ISO 7 cleanroom
SQZ Point-of-Care Manufacturing

Continued development and testing for utilization in anticipated SQZ TAC IND submission in the first half of 2023
Commenced evaluation of POC to produce additional therapeutic candidates to reduce future manufacturing-related costs; assessing the possibility of allowing access to the Cell Squeeze technology, associated methods and clinical-scale systems for manufacturing uses together with third parties
Recent Corporate Highlights

Elevated Micah Zajic to Chief Financial Officer from Chief Business Officer
Transitioned Chief Scientific Officer (CSO), Howard Bernstein, M.D., Ph.D., to the company’s Board of Directors; announced the division of CSO responsibilities among three experienced internal leaders: Ipsita Roymoulik, Ph.D., SVP, Chemistry Manufacturing and Controls; Scott Loughhead, Ph.D., VP, Translational Research; and Maisam Dadgar, Head of Engineering
Third Quarter 2022 Financial Highlights

Revenue for the quarter ended September 30, 2022, was $3.5 million compared to $4.8 million for the same period in 2021
Research and development expenses for the quarter ended September 30, 2022, were $19.6 million compared to $20.5 million for the same period in 2021; the decrease was primarily due to lower upfront manufacturing, materials and setup costs associated with the SQZ-eAPC-HPV trial
General and administrative expenses for the quarter ended September 30, 2022, were $6.9 million compared to $6.7 million for the same period in 2021; the increase was primarily due to higher personnel and other corporate-related costs, including stock-based compensation expense and other costs
Net loss for the quarter ended September 30, 2022, was $22.6 million, compared to $22.5 million for the same period in 2021
As of September 30, 2022, the Company had cash and cash equivalents of $84.2 million and anticipates this will be sufficient to fund operating expenses and capital expenditure requirements into the fourth quarter of 2023