On January 5, 2023 Integral Molecular, reported that the industry leader in antibody discovery for membrane proteins, has published the targeting mechanism enabling best-in-class specificity of its Claudin 6 (CLDN6) antibody CTIM-76 being developed for cancer therapy with Context Therapeutics (Press release, Integral Molecular, JAN 5, 2023, View Source [SID1234625899]). CLDN6 is a tumor-specific protein found in multiple solid tumors—including ovarian, endometrial, lung, gastric, and testicular—but absent from healthy adult tissues. Until now, its structural complexity and similarity to related proteins has hindered efforts to develop safe and selective therapeutics, with most CLDN6 antibody clinical trials being halted due to specificity-related safety issues. The similarity of the target to widely expressed Claudins 3, 4 and 9 means that non-specific binding could kill otherwise healthy tissues.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Publication Details

In their recent publication (Screnci et al., iScience December 2022), Integral Molecular scientists describe the isolation of highly specific CLDN6 antibodies that use a single atomic contact point centered around amino acid 156 to derive exquisite specificity. This interaction site allows the antibody to bind CLDN6 but not any of the other 24 claudin family members.

Key findings include:

Best-in-class specificity of CLDN6 antibodies compared to clinical benchmarks
Unusual steric hindrance mechanism of the gamma carbon on Q156 discovered as critical for absolute specificity of antibodies for CLDN6 versus CLDN9
CLDN6 antibodies exhibited excellent developability
"We are thrilled to be progressing high-specificity antibodies to safely target Claudin 6-positive tumors," said Ross Chambers, PhD, VP of Antibody Discovery at Integral Molecular. "The ability of our antibodies to interact specifically with Claudin 6 is extraordinary since the target and related proteins differ by just a few atoms at the binding site."

Integral Molecular’s MPS Antibody Discovery Platform is tailored to discover rare antibodies with maximal epitope diversity. Integral Molecular is co-developing CTIM-76 with Context Therapeutics to treat ovarian cancer and other solid tumors. CTIM-76 is a CLDN6xCD3 antibody that brings cytotoxic T cells into proximity with CLDN6-expressing tumor cells to initiate cell killing. Investigational New Drug (IND)-enabling studies are currently underway, and Context expects to submit an IND application for CTIM-76 to the U.S. Food and Drug Administration for first-in-human trials in the first quarter of 2024.

On January 5, 2023 Inspirna, Inc., a clinical stage biopharmaceutical company developing first-in-class small molecule cancer therapeutics, reported interim data from its ongoing Phase 1b/2 clinical trial of abequolixron in patients with non-small cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) (Press release, Inspirna, JAN 5, 2023, View Source [SID1234625898]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Abequolixron (RGX-104) is a first-in-class, small molecule liver X receptor (LXR) agonist designed to target APOE dysregulation and enhance anti-tumor immunity by inhibiting tumor angiogenesis, depleting myeloid derived suppressor cells (MDSC), and activating cytotoxic T lymphocytes (CTL). Abequolixron is currently being evaluated in a Phase 1b/2 clinical trial in combination with docetaxel in second- or third-line (2/3L) NSCLC as well as second-line (2L) SCLC. The primary objectives of the study include characterizing the safety profile and the antitumor activity of the abequolixron and docetaxel combination.

"The data thus far demonstrate that abequolixron is well tolerated in combination with full dose docetaxel, while showing encouraging clinical activity suggesting that this drug candidate could be a valuable addition to a current standard of care chemotherapy in heavily-pretreated patients with lung cancer," said Hossein Borghaei, D.O., M.S., Chief of the Division of Thoracic Medical Oncology at Fox Chase Cancer Center and Principal Investigator on the study. "I am very encouraged by the overall response rate, disease control rate, and time to progression so far seen in the study and I look forward to further evaluation of this unique compound as the clinical trial progresses."

"These data, while early, clearly show the potential that abequolixron may have in driving deep responses in patients with heavily-pretreated lung cancer," said Masoud Tavazoie, M.D., Ph.D., Chief Executive Officer of Inspirna. "We are excited to begin the new year by announcing these promising data for abequolixron and look forward to sharing more updates as we continue advancing our novel pipeline in difficult-to-treat cancers."

Key findings from the data

As of December 2, 2022, 17 patients were treated at the Recommended Phase 2 Dose (RP2D) as determined in the dose escalation stage, with 120mg abequolixron twice daily (BID), 5 days on/2 days off, plus docetaxel. Thirteen patients were evaluable for response per RECIST v1.1, including five patients with 2/3L NSCLC and eight patients with 2L SCLC.
The ORR across all evaluable patients was 38% (n=13), with a disease control rate (DCR) of 77%, including five patients who achieved partial response (PR).
In the 2/3L NSCLC cohort, of five evaluable patients, four patients achieved PRs with two patients achieving confirmed partial responses. Four of the five patients were on study treatment for > 19 weeks, including one patient for 25 weeks, one patient for 28 weeks and one ongoing patient at 37 weeks.
In the 2L SCLC cohort, of eight evaluable patients, one patient achieved a PR and five patients had a best overall response (BoR) of stable disease (SD). Four patients (50%) were on study drug progression free for > 24 weeks. One of the patients with a BoR of SD, although experiencing CNS progression at week 12, stayed on therapy for clinical benefit for 30 weeks without experiencing systemic PD.
Across the two cohorts (N=17), the most common TEAEs were fatigue in 12 patients, diarrhea and nausea in 9 patients, decreased appetite in 8 patients and neutropenia and weight loss in 7 patients. Of the most common TEAEs, Grade 4 events were neutropenia (2 patients) and Grade 3 events were fatigue (2 patients), diarrhea (1 patient), nausea (1 patient), decreased appetite (1 patient) and the others were Grade < 2.
The expansion stage of the study is ongoing and continues to enroll patients with 2/3L NSCLC. In addition, this Phase 1b/2 study includes an ongoing expansion arm of abequolixron in combination with Yervoy (ipilimumab) in second- or third-line endometrial cancer as part of a clinical collaboration with Bristol Myers Squibb.

About Abequolixron (RGX-104)

Abequolixron is an orally administered small molecule agonist of the Liver X Receptor (LXR) which activates expression of the APOE tumor suppressor protein. APOE expression becomes dysregulated (silenced) in the tumors of select patients with solid cancers. APOE dysregulation results in increased tumor angiogenesis (tumor blood vessel growth) as well as a shifting of the tumor myeloid cell population from immune-stimulatory to immune-suppressive, which are both counteracted by abequolixron. Abequolixron is currently being tested in a Phase 1b/2 clinical trial in combination with standard-of-care regimens in several lung cancer indications that are enriched for APOE dysregulation, including SCLC and NSCLC.

On January 5, 2023 Lipocine presented its corporate presentation (Presentation, Lipocine, JAN 5, 2023, View Source [SID1234625902]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

On January 5, 2023 iBio, Inc. (NYSEA:IBIO) ("iBio" or the "Company"), an AI-driven innovator of precision antibody immunotherapies, reported that the United States Patent and Trademark Office has issued U.S. Patent No. 11,545,238, entitled "Machine Learning Method For Protein Modelling To Design Engineered Peptides," which covers a machine learning model developed to design engineered epitopes which allow precise steering of therapeutic antibodies towards specific regions of a target protein (Press release, iBioPharma, JAN 5, 2023, https://ir.ibioinc.com/news-events/press-releases/detail/201/ibio-announces-issuance-of-u-s-patent-covering [SID1234625897]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are thrilled to be issued this U.S. patent, which solidifies our position as a leader in AI-driven drug discovery, and whose claims guarantee broad coverage of our proprietary, epitope-steering antibody discovery engine," said Martin Brenner, DVM. Ph.D., iBio’s Chief Scientific Officer. "In addition to marking an important milestone as we transform iBio into an AI-powered biotech company, this patent provides us with a competitive advantage as we continue to build our differentiated pipeline, with benefits that extend to our potential future partners."

iBio’s RubrYc Discovery Engine is designed to tackle complex and challenging drug targets with the goal of developing safer and more effective immunotherapies for difficult-to-treat cancers. It uses a combination of a proprietary epitope steering technology, a specialized antibody library, and AI-powered antibody optimization to quickly identify and optimize molecules that can effectively address challenging drug targets. This allows for faster discovery compared to traditional antibody discovery methods.

On January 5, 2023 Genprex, Inc. ("Genprex" or the "Company") (NASDAQ: GNPX), a clinical-stage gene therapy company focused on developing life-changing therapies for patients with cancer and diabetes, reported that it has entered into an exclusive license agreement (the Agreement) with the University of Pittsburgh (Pitt), granting Genprex a worldwide, exclusive license to a patent application and related technology and a worldwide, non-exclusive license to use certain related know-how, all related to gene therapy for Type 2 diabetes using the genes of the Pdx1 and MafA transcription factors (Press release, Genprex, JAN 5, 2023, View Source [SID1234625896]). The preclinical technology, GPX-003, is believed to work by rejuvenating diminished beta cells to increase insulin expression by introducing transcription factors controlled by an insulin promoter.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"This marks the Company’s third technology license this year supporting our diabetes program, demonstrating the continued strengthening of our intellectual property portfolio, our diabetes program, and our position as a lead innovator in emerging diabetes gene therapies," said Rodney Varner, President and Chief Executive Officer of Genprex. "We are thrilled to have secured multiple cutting edge technologies from Pitt that expand our diabetes gene therapy program and specifically target Type 1 and Type 2 diabetes."

"With this license agreement, Genprex now has a drug product candidate for Type 1 diabetes, GPX-002, that uses a glucagon promoter specifically optimized for use in alpha cells and another drug product candidate, GPX-003 for Type 2 diabetes, that uses an insulin promoter optimized for beta cells," said Mark Berger, MD, Chief Medical Officer of Genprex. "Both product candidates are based on the same general gene therapy approach under Genprex’s original license that is comprised of a novel infusion process that uses an endoscope and an adeno-associated virus (AAV) vector to deliver Pdx1 and MafA genes directly to the pancreas. Each of these technologies may have the potential to provide long-term efficacy and to change the course of this disease for the millions of patients around the world with diabetes."

All of the diabetes technologies licensed from Pitt by Genprex are out of the laboratory of George Gittes, MD, Professor of Surgery and Pediatrics and Chief of the Division of Pediatric Surgery at the University of Pittsburgh School of Medicine.

Genprex recently announced a license agreement with the University of Pittsburgh for a preclinical technology that transforms macrophages enabling them to reduce autoimmune activity in Type 1 diabetes, a technology that could be complementary to the Company’s GPX-002 diabetes technology.

In models of Type 1 diabetes, GPX-002 transforms alpha cells in the pancreas into functional beta-like cells, which can produce insulin but are distinct enough from beta cells to evade the body’s immune system. GPX-003 for Type 2 diabetes, where autoimmunity is not at play, is believed to rejuvenate and replenish exhausted beta cells.

Earlier studies in diabetic mouse models showed that an earlier version of GPX-002 restored normal blood glucose levels for an extended period of time, typically around four months. It is believed that the duration of restored blood glucose levels in mice could translate to decades in humans. Preliminary data from a more recent study in a non-human primate model of Type 1 diabetes also have been promising and are expected to be presented at a scientific meeting during the first quarter of 2023.

More than 537 million people around the world have diabetes, and in the U.S. alone, there are 37.3 million people with diabetes. In 2021, diabetes took the lives of more than 6.7 million people.