On January 16, 2024 Ferring Pharmaceuticals reported that ADSTILADRIN (nadofaragene firadenovec-vncg) is now fully available across the U.S. for healthcare providers to prescribe for their adult patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors (Press release, Ferring, JAN 16, 2024, View Source [SID1234639258]). Approved by the U.S. Food & Drug Administration (FDA) in December 2022, ADSTILADRIN is the first and only FDA-approved intravesical gene therapy for adults with NMIBC who no longer respond to standard therapy.

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"From the day we received FDA approval, Ferring has been committed to making
ADSTILADRIN available to every appropriate high-risk NMIBC patient quickly and responsibly, working collaboratively with the bladder cancer community to inform our approach," said Bipin Dalmia, Senior Vice President, Global Head, Uro-Oncology Franchise at Ferring Pharmaceuticals. "With our significant manufacturing investments, we have achieved full product supply ahead of schedule. We are therefore ending our ADSTILADRIN Early Experience Program and look forward to bringing this novel therapy to every patient who needs it"

In September 2023, Ferring initiated the ADSTILADRIN Early Experience Program to a mix of clinical trial sites that participated in the ADSTILADRIN Phase 3 study and community clinics with the highest number of appropriate patients with NMIBC. This temporary program represented Ferring’s commitment to treat as many patients as possible in the short term while ensuring every patient who started on ADSTILADRIN had the ability to continue therapy for the duration of their treatment. Now that full product supply is available ahead of schedule, Ferring can end the temporary ADSTILADRIN Early Experience Program and dramatically increase patient access.

"ADSTILADRIN represents an effective alternative therapy for patients with NMIBC who, historically, had very few options once they no longer responded to standard BCG therapy," said Andrea Maddox-Smith, CEO of the Bladder Cancer Advocacy Network, BCAN. "Increasing access to this innovative therapy offers the potential of what patients need most – safe, effective treatment options that bring hope."

Ferring also initiated a non-interventional study, known as the "ADSTILADRIN in BLadder
CancEr" (ABLE-41) U.S. Real World Evidence (RWE) Study (NCT06026332). This ongoing
study is exploring early utilization, experiences, and outcomes of ADSTILADRIN in the routine care setting.

About ADSTILADRIN
ADSTILADRIN (nadofaragene firadenovec-vncg) is the first and only FDA-approved
intravesical gene-therapy for the treatment of adult patients with high-risk Bacillus CalmetteGuérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors. It is a non-replicating adenovirus vector-based therapy containing the gene interferon alfa-2b, administered by catheter directly into the bladder once every three months. The vector enters the cells of the bladder wall, releasing the active gene and causing the bladder’s cell walls to secrete high quantities of interferon alfa-2b protein, a naturally-occurring protein the body uses to fight cancer. This approach essentially turns the bladder wall cells into interferon microfactories, enhancing the body’s own natural defenses against the cancer.

ADSTILADRIN has been studied in a clinical trial program that includes 157 patients with highgrade, BCG-unresponsive NMIBC who had been treated with adequate BCG previously and did not see benefit from additional BCG treatment (full inclusion criteria published on
clinicaltrials.gov: NCT02773849).1

About Non-Muscle Invasive Bladder Cancer (NMIBC)
NMIBC is a form of bladder cancer which is present in the superficial layer of the bladder and has not invaded deeper into the bladder or spread to other parts of the body.2
Bladder cancer is the sixth most common cancer in the U.S., and it is estimated that there were approximately 81,180 new cases of bladder cancer in the U.S. in 2022,3
75% of which present as NMIBC.4 In patients with high-risk NMIBC, intravesical BCG remains the first-line standard of care. However, more than 50% of patients who receive initial treatment with BCG will experience disease recurrence and progression within one year, with many developing BCG-unresponsive disease.3 Current treatment options for BCG-unresponsive patients are very limited, and National Comprehensive Cancer Network (NCCN) guidelines recommend cystectomy (partial or complete removal of the bladder).5

INDICATION
ADSTILADRIN is a non-replicating adenoviral vector-based gene therapy indicated for the
treatment of adult patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive nonmuscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors.

IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS: ADSTILADRIN is contraindicated in patients with prior hypersensitivity reactions to interferon alfa or to any component of the product.

WARNINGS AND PRECAUTIONS:

Risk with delayed cystectomy: Delaying cystectomy in patients with BCG-unresponsive CIS could lead to development of muscle invasive or metastatic bladder cancer, which can be lethal. If patients with CIS do not have a complete response to treatment after 3 months or if CIS recurs, consider cystectomy.
Risk of disseminated adenovirus infection: Persons who are immunocompromised or immunodeficient may be at risk for disseminated infection from ADSTILADRIN due to low levels of replication-competent adenovirus. Avoid ADSTILADRIN exposure to immunocompromised or immunodeficient individuals.
DOSAGE AND ADMINISTRATION: Administer ADSTILADRIN by intravesical instillation only. ADSTILADRIN is not for intravenous use, topical use, or oral administration.

USE IN SPECIFIC POPULATIONS: Advise females of reproductive potential to use effective contraception during ADSTILADRIN treatment and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during ADSTILADRIN treatment and for 3 months after the last dose.

ADVERSE REACTIONS: The most common (>10%) adverse reactions, including laboratory abnormalities (>15%), were glucose increased, instillation site discharge, triglycerides increased, fatigue, bladder spasm, micturition (urination urgency), creatinine increased, hematuria (blood in urine), phosphate decreased, chills, pyrexia (fever), and dysuria (painful urination).

You are encouraged to report negative side effects of prescription drugs to FDA. Visit www.FDA.gov/medwatch or call 1-800-332-1088. You may also contact Ferring Pharmaceuticals at 1-888-FERRING.

Please click to see the full Prescribing Information.

On January 16, 2024 MEI Pharma, Inc. (Nasdaq: MEIP), a clinical-stage pharmaceutical company evaluating novel drug candidates to address known resistance mechanisms to standard-of-care cancer therapies, reported the design of the ongoing Phase 1b study of the mitochondrial oxidative phosphorylation (OXPHOS) inhibitor ME-344 in combination with bevacizumab (Avastin) in refractory metastatic colorectal cancer patients will be presented during a poster session at the 2024 ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium to be held January 18 – 20, 2024 (Press release, MEI Pharma, JAN 16, 2024, View Source [SID1234639278]).

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Presentation Title: A Phase 1b Study of the OXPHOS Inhibitor ME-344 in Combination with Bevacizumab in Refractory Metastatic Colorectal Cancer
Session Title: Trials in Progress Poster Session C: Cancers of the Colon, Rectum, and Anus
Presenter: Patrick M. Boland
Date: Saturday, January 20, 2024, 6:30-7:45 AM (Pacific Time)
Abstract Number: TPS222

The poster can be viewed on the MEI Pharma website here:
View Source

About the Phase 1b Study

The ongoing Phase 1b study is evaluating ME-344 plus bevacizumab across two cohorts in patients with metastatic colorectal cancer after failure of standard therapies. The combination of ME-344 and bevacizumab is intended to create metabolic synthetic lethality by leveraging the ability of antiangiogenics like bevacizumab to reduce glycolysis, forcing tumors to switch to mitochondrial respiration via OXPHOS, which is inhibited by ME-344.

In the first cohort of approximately 20 patients ME-344 is administered at 10 mg/kg once weekly for 3 weeks in combination with bevacizumab every two weeks, with cycles repeated every 4 weeks. If the rate of non-progression in Cohort 1 reaches a predetermined progression free survival threshold, Cohort 2 will enroll an additional 20 patients. Patients will be treated until disease progression or intolerability. The primary endpoint of the study is progression free survival. Secondary endpoints include overall response rate, duration of response, overall survival and safety.

The study is being conducted at member centers of the Academic GI Cancer Consortium (AGICC), an oncology consortium dedicated to identifying new drugs to treat gastrointestinal (GI) cancers.

About ME-344

ME-344 is a novel drug candidate that inhibits mitochondrial oxidative phosphorylation (OXPHOS), a fundamental metabolic pathway involved in the production of adenosine triphosphate (ATP) in the mitochondria. ATP provides energy to drive many metabolic cell processes, including division, proliferation, and growth. By disrupting the production of ATP, ME-344 has been shown to induce cancer cell death in nonclinical models and was associated with antitumor activity in clinical studies.

The two main sources of ATP production in cells are OXPHOS and glycolysis; the latter is highly active in most tumors. Anti-angiogenics, like the vascular endothelial growth factor (VEGF) inhibitor bevacizumab (AVASTIN), have the potential to normalize vasculature and decrease reliance on glycolysis. The resulting reduction in glycolysis may trigger an increased dependence on mitochondrial ATP production for energy to support continued tumor proliferation.

In such cases of tumor plasticity, the combination of ME-344 and bevacizumab may induce metabolic synthetic lethality, providing a novel therapeutic strategy. Specifically, leveraging the ability of antiangiogenics like bevacizumab to reduce glycolysis and force tumor cells to switch to mitochondrial respiration via OXPHOS, which is inhibited by ME-344, may reduce access to ATP needed for cell division and growth in tumors.

This approach was first clinically evaluated in a multicenter, investigator-initiated, randomized, open-label, window of opportunity clinical study, evaluating ME-344 (3 doses) plus bevacizumab (1 dose) in 42 women with early HER2-negative breast cancer. Study results demonstrated significant biological antitumor activity as measured by a reduction in the proliferative biomarker Ki-67 compared to placebo. The combination appeared to be generally well tolerated. The data from this study were consistent with preclinical data suggesting that combining ME-344 can augment anti-angiogenic therapy and provided validation for continued evaluation of the combination of ME-344 with bevacizumab and other VEGF inhibitors.

An earlier Phase 1 clinical study evaluating ME-344 as a single-agent in patients with refractory solid tumors also demonstrated anti-tumor activity, further validating the potential of mitochondrial inhibition as a promising therapeutic modality.

On January 16, 2024 iBio, Inc. (NYSEA:IBIO) ("iBio" or the "Company"), an AI-driven innovator of precision antibody immunotherapies, reported that Matthew P. Greving Ph.D., its Vice President and Head of Platform Technologies and Machine Learning, will give a podium presentation titled "Enhancing Bispecific T-Cell Engager Discovery, Potency, Safety, and Developability with Machine Learning and Mammalian Display" at the 23rd annual PepTalk Conference Jan. 16-19 in San Diego, California (Press release, iBioPharma, JAN 16, 2024, View Source [SID1234639259]). He will also moderate a BuzZ talk on the topic as part of the conference’s "Developability of Bispecifics" program.

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During the podium presentation, Dr. Greving will provide an overview of how iBio’s technology stack – including epitope engineering, human-diversity antibody libraries, EngageTx for bispecific optimization, and ShieldTx for antibody masking – potentially overcomes challenges in the discovery of bispecific T-Cell Engagers ("TCE"), a promising area of research in immunotherapies for cancer. He will present data demonstrating how iBio’s machine learning (ML)-driven epitope steering and mammalian-display antibody libraries efficiently discover diverse TCE arms tuned for potency, toxicity, developability, and cyno cross-reactivity. The presentation will take place Tuesday, Jan. 16 at 5:15 p.m. Pacific Time.

Before the presentation, Dr. Greving will moderate an informal, open discussion diving into topics including, but not limited to, improving discovery and productivity for bispecific TCE’s immune cell arm, advances in discovering difficult tumor-antigen arm targets and epitopes, enhancing T-cell engager safety with machine-learning derived mammalian display libraries, and large-scale bispecific activity and developability screening with mammalian display. The BuzZ session will occur on Tuesday, Jan. 16, at 3:15 p.m. Pacific Time.

iBio’s Drug Discovery Platform is a precision-driven and deeply integrated technology stack that aims to efficiently and consistently deliver antibody candidates against challenging targets and move them into the clinic faster. The Company uses its technology to advance candidates with partners and collaborators, and for its own proprietary pipeline.

On January 16, 2024 Promega reported that a research published today in Nature Communications demonstrates a new potential approach for managing multiple myeloma and other hematological cancers (Press release, Promega, JAN 16, 2024, View Source [SID1234639279]). The molecule, called SJ3149, demonstrates potent anti-proliferative activity in a variety of human cancer cell lines through selective degradation of the cancer-causing protein CK1α. The authors suggest that this degrader shows great promise for broad-spectrum anti-cancer applications.

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"The rapid and robust degradation of CK1α affects the target’s cellular pathway, leading to broad killing in a variety of cancer cell models," says Promega Research Scientist Elizabeth Caine. "We believe the research in this paper will provide valuable insights to researchers developing all types of degrader molecules."

Targeted protein degradation is an emerging form of treatment in which a therapeutic molecule recruits the cell’s own machinery to destroy defective proteins. In this study, the team primarily focused on degrading a protein called CK1α, which is linked to uncontrolled cell proliferation. They report that SJ3149 potently and selectively degrades CK1α and limits the proliferation of multiple cancer cell lines spanning a wide range of disease subtypes. Their results strongly support future research on applying selective CK1α degraders to many different cancer types.

Promega scientists collaborated with researchers at St. Jude Children’s Research Hospital on this study. The paper is available open access from Nature Communications at View Source

Learn more about how Promega technologies are used to study targeted protein degradation here.

On January 16, 2024 Adagene Inc. ("Adagene") (Nasdaq: ADAG), a company transforming the discovery and development of novel antibody-based therapies, reported data from its presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2024 Gastrointestinal (GI) Cancers Symposium, taking place January 18-20 in San Francisco (Press release, Adagene, JAN 16, 2024, View Source [SID1234639974]).

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"The expanded therapeutic index for the masked ADG126 allows us to dose with a higher and more frequent effective dose of anti-CTLA-4 therapy than today’s options," said Daneng Li, MD and Associate Professor Department of Medical Oncology & Therapeutics Research at the City of Hope Comprehensive Cancer Center. "These promising data support further evaluation of this potential best-in-class anti-CTLA-4 antibody, ADG126, in combination with pembrolizumab for MSS CRC patients, including battling new liver lesions in those patients initially without detectable liver metastasis. We also see a tremendous opportunity to help patients in other tumor types where there is a significant need for safe and potent anti-CTLA-4 therapy."

Key highlights from the poster (November 30, 2023 data cutoff) include:

Results from dose escalation and dose expansion cohorts of ADG126 in combination with Merck & Co., Inc., Rahway, NJ, USA’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) (200 mg/Q3W) demonstrated a best-in-class safety profile for ADG126 at doses from 6 mg/kg to 10 mg/kg in heavily pre-treated advanced/metastatic patients (N=46):
Limited dose-dependent toxicities were observed.
Grade 3 TRAEs occurred in 5/46 patients (10.8%), with no Grade 4 or 5 TRAEs and a discontinuation rate of 6.5% (3/46).
In dose escalation across tumor types, two partial confirmed responses (PRs) were observed among the three patients treated with ADG126 10 mg/kg Q3W, which triggered expansion cohorts at this dosing regimen. One of the patients had PD-1 refractory cervical cancer and the other had endometrial cancer. Both confirmed PRs are sustained after more than 55 weeks (over 14 cycles) of treatment.
In dose expansion of patients with MSS CRC, 12 evaluable patients without liver metastases were treated at the active, potent dose of 10 mg/kg Q3W:
Two confirmed PRs were observed in nine of these patients without peritoneal and liver metastases, resulting in an overall response rate of 22% in this subset.
An additional seven of these nine patients experienced stable disease (SD) for an overall disease control rate 100% (2 PRs and 7 SD).
Observation of these clinical activities triggered further expansion into Stage 2 of the Simon’s 2-stage design for this dose level, which is currently ongoing with data anticipated throughout 2024.
In a preliminary PFS analysis of those MSS CRC patients free of liver and peritoneal metastasis, a median PFS of seven months was observed in those treated with ADG126 10 mg/kg at two dosing frequencies pooled together [every three weeks (n=9) and every six weeks (n=6)]. The durable clinical activity of ADG126 in combination with pembrolizumab will continue to be evaluated as a larger cohort of subjects becomes evaluable at the 10 mg/kg Q3W dose level.
Commenting on the results, Heinz Josef-Lenz, MD, FACP, Associate Director for Clinical Research and Co-leader of the Translational Science Program at the USC Norris Comprehensive Cancer Center (NCCC) said, "I believe that CTLA-4 is an essential part of an effective immunotherapy for MSS CRC, yet physicians have been limited by the safety challenges from first generation options. The clinical profile of ADG126 in combination with pembrolizumab presents a great opportunity for MSS CRC patients that otherwise have limited immunotherapy options available."

ASCO-GI Poster Presentation Details

Title: Results of a phase 1b/2 study of ADG126 (a masked anti-CTLA-4 SAFEbody) in combo with pembrolizumab (Pembro) in patients (Pts) with metastatic microsatellite-stable (MSS) colorectal cancer (CRC)

Date: Saturday, January 20
Time: 6:30 a.m. – 7:55 a.m. Pacific Time
Onsite Location: Moscone West
Abstract Number: 127
Poster Board: H12
Consistent with the ASCO (Free ASCO Whitepaper)-GI embargo policy, the data are being released today in conjunction with the abstract publication.

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