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 Delcath Systems, Inc. (Nasdaq: DCTH), an interventional oncology company focused on the treatment of primary and metastatic cancers of the liver, reported the first commercial use of HEPZATO KIT for the treatment of metastatic uveal melanoma (mUM) (Press release, Delcath Systems, JAN 16, 2024, https://delcathsystemsinc.gcs-web.com/news-releases/news-release-details/delcath-systems-announces-us-launch-and-first-commercial [SID1234639256]).

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The procedure took place at Moffitt Cancer Center in Tampa, Florida by Dr. Jonathan S. Zager, M.D., Chief Academic Officer; Senior Member, Department of Cutaneous, Oncology; Director of Regional Therapies, Moffitt Cancer Center. Dr. Zager was the global Lead Investigator for the FOCUS Phase 3 trial.

"The fact that patients with difficult to treat metastatic uveal melanoma with limited treatment options now have another alternative is truly remarkable and exciting. There has been a large unmet need for liver directed therapy options to treat this patient population and we intend to incorporate this as standard of care for appropriate patients," said Dr. Zager. Dr. Zager enrolled and treated the first and last patients on the FOCUS Phase 3 trial and the team at Moffitt has performed the procedure over 200 times to date.

The company is working with numerous other leading cancer centers across the U.S. which have indicated interest in HEPZATO KIT to ensure patients nationwide have access to this important treatment. In conjunction with the first commercial treatment, Delcath also launched websites relating to the HEPZATO KIT, including HEPZATO KIT, HEPZATO KIT REMS, and HEPZATO KIT Access, to support the commercial launch.

"The first commercial procedure utilizing HEPZATO KIT in the U.S. is a significant milestone for Delcath and patients suffering from metastatic uveal melanoma. We are proud to continue our relationship with Dr. Zager and the team at Moffitt Cancer Center to bring this unique treatment to appropriate patients in need. I want to thank all the collaborators and patients who participated in the long but necessary process to bring HEPZATO KIT to market," said Gerard Michel, Delcath’s Chief Executive Officer.

About HEPZATO KIT

HEPZATO KIT (melphalan for Injection/Hepatic Delivery System), approved for use in the United States by FDA, is a combination drug/device product which administers HEPZATO (melphalan) directly to the liver through the HDS, which permits higher drug exposure in target tissues while limiting systemic toxicity.

HEPZATO KIT is approved in the United States as a liver-directed treatment for adult patients with uveal melanoma with unresectable hepatic metastases affecting less than 50% of the liver and no extrahepatic disease, or extrahepatic disease limited to the bone, lymph nodes, subcutaneous tissues, or lung that is amenable to resection or radiation.

HEPZATO KIT Important Safety Information
Patients eligible for HEPZATO KIT should NOT have any of the following medical conditions:

Active intracranial metastases or brain lesions with a propensity to bleed
Liver failure, portal hypertension, or known varices at risk for bleeding
Surgery or medical treatment of the liver in the previous 4 weeks
Active cardiac conditions including unstable or severe angina or myocardial infarction), worsening or new-onset congestive heart failure, significant arrhythmias, or severe valvular disease
History of allergies or known hypersensitivity to melphalan or a component or material utilized within the HEPZATO KIT including natural rubber latex, heparin, and severe hypersensitivity to iodinated contrast not controlled by antihistamines and steroids
Most common adverse reactions or laboratory abnormalities occurring with HEPZATO KIT treatment are thrombocytopenia, fatigue, anemia, nausea, musculoskeletal pain, leukopenia, abdominal pain, neutropenia, vomiting, increased alanine aminotransferase, prolonged activated partial thromboplastin time, increased alkaline phosphatase, increased aspartate aminotransferase and dyspnea.

Severe peri-procedural complications including hemorrhage, hepatocellular injury, and thromboembolic events may occur via hepatic intra-arterial administration of HEPZATO. HEPZATO KIT is available only through a restricted program under a Risk Evaluation and Mitigation Strategy called the HEPZATO KIT REMS. Myelosuppression with resulting severe infection, bleeding, or symptomatic anemia may occur with HEPZATO. Additional cycles of HEPZATO KIT therapy will be delayed until blood counts have improved.

Please see the full Prescribing Information, including BOXED WARNING for the HEPZATO KIT.

On January 16, 2024 Celyad Oncology (Euronext: CYAD) (the "Company"), reported a fourth quarter 2023 business update and an outlook for 2024 (Press release, Celyad, JAN 16, 2024, View Source [SID1234639255]).

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Michel Lussier, interim Chief Executive Officer of Celyad Oncology, commented: "2023 has been a very important year for Celyad Oncology, after the changes that occurred in 2022. Our research team has made a remarkable progress to broaden the range of cancer indications that could be targeted by chimeric antigen receptor (CAR) T-cells and to tackle the main limitations of current CAR T-cell therapies. We have shared new data at several scientific and business conferences along the year, and published in high impact peer-reviewed journals. We are eager to see the impact of our efforts to unleash the power of our IP estate and stay at the forefront of next-generation CAR T-cell development."

2023 corporate accomplishments

On August 24, 2023, the Company announced that it obtained commitments from Fortress, Tolefi and other longstanding existing shareholders to subscribe to a capital increase of up to €9.8 million in 2 tranches:
A first tranche of 2.0 million was disbursed in the context of authorized capital as of September 4, 2023; and
A second tranche subscribed by Fortress was approved by the extraordinary shareholders’ meeting of November 14, 2023. Following this private placement, the Company believes that its existing cash and cash equivalents should be sufficient, based on the current scope of activities, to fund operating expenses and capital expenditure requirements into the second quarter of 2025.
2023 operational highlights

Multiplex short hairpin ribonucleic acid (shRNA) non-gene edited technology – All along 2023, we have collected and presented data validating our shRNA multiplexing approach:
We developed a chimeric micro-RNA (miRNA) cluster to enable multiplexing of shRNAs, designed for easy, efficient, and tunable downregulation of up to four target genes simultaneously in CAR T-cells;
Results detailing the technical aspects of the development of this platform have been published in Molecular Therapy – Nucleic Acids (Mol Ther Nucleic Acids. 2023, 34:102038). This publication has raised much interest from the community and was subjected to an editorial comment in the same volume of the Journal (Mol Ther Nucleic Acids. 2023, 34:102077);
Additional data which demonstrate feasibility of this approach in the context of allogeneic cell therapies or with the aim to create therapies able to overcome the coinhibitory effects of exhaustion markers were presented at several scientific conferences. Posters are available on the company’s website, at View Source
Multispecific NKG2D-based CAR T-cell platform – In 2023, we have compiled and presented data validating our multispecific approach targeting NKG2D ligands (NKG2DL):
We have developed different CD19/NKG2DL, BCMA/NKG2DL and PSMA/NKG2DL multispecific CAR T-cells, utilizing both tandem constructs – that encompass the extracellular domain of the natural NKG2D receptor fused to a scFv targeting CD19, BCMA or PSMA, or dual constructs – that co-express the NKG2D-based CAR with an anti-CD19, anti-BCMA or anti-PSMA CAR, respectively;
Our data provides the proof-of-concept that NKG2DL are valuable targets in a multispecific CAR approach and demonstrate our CD19/NKG2DL multispecific CAR T-cells are highly effective to counteract relapses due to CD19 antigen loss in vivo. In vitro data generated with BCMA/NKG2DL and PSMA/NKG2DL multispecific CAR T-cells further validate this approach in other hematological and solid indications. Posters are available on the company’s website, at View Source
Financial highlights

As of December 31, 2023, the Company had cash and cash equivalents of €3.0 million and short-term investments of €4.0 million. The Company projects that its existing cash, cash equivalents and short-term investments should be sufficient to fund operating expenses and capital expenditure requirements into the second quarter of 2025. Therefore, the Company continues to project that its existing cash and cash equivalents will be sufficient to fund its estimated operating and capital expenditures over at least the next 12 months from the date of this press release.

Outlook for 2024

More data and evidence in the context of the multispecific CAR T-cell platform and shRNA multiplexing approach will be shared in the first half of 2024, with the aim to develop assets ready for a potential initiation of clinical trials either by the Company and/or through strategic partnerships afterwards.
Celyad Oncology will attend the 7th CAR-TCR Europe summit in London, UK (February 27-29, 2024), the must-attend forum to brainstorm and stay at the forefront of cell therapy innovations.
Financial Calendar 2024

April 5th, 2024 Full Year 2023 Financial Results
May 6th, 2024 Annual shareholders meeting
August 6th, 2024 First Half 2024 Interim Results
The financial calendar is communicated on an indicative basis and may be subject to change.

On January 16, 2024 Cellectis (Euronext Growth: ALCLS – NASDAQ: CLLS) (the "Company"), a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies, reported that it has drawn down the second tranche of €15 million ("Tranche B") under the credit facility agreement for up to €40 million entered into with the European Investment Bank (the "EIB) on December 28, 2022 (the "Finance Contract") (Press release, Cellectis, JAN 16, 2024, View Source [SID1234639254]). Tranche B is expected to be disbursed by the EIB by January 25, 2024. The Company plans to use the proceeds of Tranche B towards the development of its pipeline of allogeneic CAR T-cell product candidates: UCART22, UCART20x22, and UCART123.

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As a condition to the disbursement of Tranche B the Company issued 1,460,053 warrants to the benefit of the EIB, in accordance with the terms of the 14th resolution of the shareholders’ meeting held on June 27, 2023 and articles L. 228-91 and seq. of the French Commercial Code (the "Tranche B Warrants").

Each Tranche B Warrant allows the EIB to subscribe for one ordinary share of the Company, at a price of €2.53, corresponding to 99% of the volume-weighted average price of the Company’s ordinary shares over the last 3 trading days preceding the decision of the board of directors of the Company to issue the Tranche B Warrants. The total number of shares issuable upon exercise of the Tranche B Warrants represents circa 2% of the Company’s outstanding share capital as at their issuance date.

Tranche B will mature six years from its disbursement date and will accrue interest at a rate of 7% per annum capitalized annually and payable at maturity.

The other terms of the Tranche B Warrants and prepayment events of Tranche B under the Finance Contract are as set forth in the Company’s press release of April 4, 2023 and Form 6-K filed with the U.S. Securities and Exchange Commission on such date.

The Finance Agreement allows the Company to drawdown a third tranche, of a maximum amount of €5 million, subject to certain conditions, including issuance of a specified number of additional warrants to the benefit of the EIB.

On January 16, 2024 BullFrog AI Holdings, Inc. (NASDAQ: BFRG; BFRGW) ("BullFrog AI" or the "Company"), a technology-enabled drug development company using artificial intelligence (AI) and machine learning to enable the successful development of pharmaceuticals and biologics, reported that the Australian Patent Office has issued Patent No. 2019216757 protecting the Company’s novel prodrugs derived from mebendazole and their use in treating cancers and other diseases (Press release, Bullfrog AI, JAN 16, 2024, View Source [SID1234639253]). This follows the July 2023 announcement of the issuance of U.S. Patent No. 11,712,435 for this invention (link), with issuance of patents expected in additional territories in the future.

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The patented compounds exhibit improved solubility and oral bioavailability relative to the parent drug, thereby addressing a key difficulty associated with the potential use of mebendazole for oncology indications, and include BF-223, a key asset in the Company’s pipeline of in-licensed drugs. The Company previously announced positive results from a preclinical study demonstrating that BF-223 has anticancer activity in an animal model for glioblastoma (link).

"This patent grant further strengthens intellectual property protection of this key asset in our pipeline," said Vin Singh, founder and CEO of BullFrog AI. "Mebendazole has shown promise in treating various types of cancer, and the results of our preclinical study evaluating BF-223 in an animal model of glioblastoma support our thesis that prodrugs of mebendazole may provide enhanced therapeutic potential, thereby improving the likelihood of clinical success. We look forward to working with strategic partners to monetize this promising asset for the treatment of glioblastoma and other oncology indications."