On April 18, 2024 Ferring Pharmaceuticals and SK pharmteco reported an agreement to scale up commercial manufacturing capacity for the drug substance of Ferring’s intravesical gene therapy Adstiladrin (nadofaragene firadenovec-vncg) for ensuring long-term future supply (Press release, Ferring, APR 18, 2024, https://www.ferring.com/ferring-pharmaceuticals-and-sk-pharmteco-enter-into-commercial-gene-therapy-manufacturing-deal/ [SID1234642150]). Following technology transfer, SK pharmteco, a contract development manufacturing organisation (CDMO), will be qualified as another source for manufacturing, testing, and release of the medicine, subject to regulatory approval by the U.S. Food and Drug Administration (FDA).

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Adstiladrin was approved by the FDA in December 2022 for 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.

This additional scale up and diversification of drug substance capacity demonstrates Ferring’s commitment to securing future long-term supply of Adstiladrin to meet the projected commercial growth of its non-replicating gene therapy. In addition to this contract manufacturing agreement, dedicated capacity expansion of Adstiladrin is well underway at state-of-the-art facilities in Ferring’s existing site in Finland and its U.S. campus in Parsippany, New Jersey. Ferring will provide updates on the progress of these near-term projects later in 2024.

"Ferring takes its responsibilities to patients with high-risk BCG-unresponsive NMIBC very seriously – especially when pioneering in the emerging field of gene therapy commercial manufacturing," said Bipin Dalmia, Global Head, Uro-Oncology Franchise, Ferring Pharmaceuticals. "Following our January announcement of full availability of Adstiladrin across the U.S. and expansion of our clinical trials program, this agreement with SK pharmteco comes alongside major investments in our own manufacturing capabilities to assure the breadth of our long-term supply base. Stable and sustainable supply is a vital part of our mission to fill this unmet clinical need for the patients we serve."

The need to scale up supply of strategically important medicines for bladder cancer across geographies is demonstrated by the trend of increased disease prevalence worldwide. The World Bladder Cancer Patient Coalition has reported that bladder cancer became the ninth most common cancer in the world (a rise from tenth) according to new data published in February 2024 (IARC GLOBOCAN 2022)1. In the United States, it is the seventh most common cancer, fourth among men, 2-3 and 75% of bladder cancer presents as NMIBC.4

"SK pharmteco is proud to partner with Ferring Pharmaceuticals as a manufacturer of the breakthrough gene therapy Adstiladrin," said Joerg Ahlgrimm, Chief Executive Officer for SK pharmteco. "Our integrated approach, incorporating customizable clinical and commercial GMP manufacturing solutions with comprehensive in-process testing, quality control, and lot release programs, provides unparalleled support to our partners throughout their product lifecycle and is in perfect alignment with our mission of expediting the delivery of potentially life-saving therapies to patients across the globe."

SK pharmteco was selected based on their competencies and alignment on core values across the two companies following a thorough assessment of potential CDMOs with gene therapy development and GMP manufacturing capabilities.

About Adstiladrin
Adstiladrin (nadofaragene firadenovec-vncg) is a gene therapy developed as a treatment for adult patients with BCG-unresponsive NMIBC. It is a non-replicating adenovirus vector-based gene therapy containing the gene encoding interferon alfa-2b protein, administered by catheter into the bladder once every three months. The vector enters the cells of the bladder wall, releasing the interferon gene. The internal cell machinery translates the interferon DNA sequence, resulting in the cells secreting high quantities of interferon alfa-2b protein, a recombinant analog of the naturally occurring protein the body uses to fight cancer. This novel gene therapy approach thereby turns the patient’s own bladder wall cells into interferon microfactories, enhancing the body’s natural defenses against the cancer. Nadofaragene firadenovec-vncg has been studied in a clinical trial program that includes 157 patients with high-grade, 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).

Nadofaragene firadenovec-vncg has been studied in a clinical trial program that includes 157 patients with high-grade, 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).4

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 non-muscle 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 April 18, 2024Bio-Path Holdings, Inc., (Nasdaq: BPTH) (the "Company" or "BioPath"), a biotechnology company leveraging its proprietary DNAbilize antisense RNAi nanoparticle technology to develop a portfolio of targeted nucleic acid cancer drugs, reported that it has entered into a definitive agreement with certain institutional investors for the issuance and sale of 375,000 shares of its common stock at a purchase price per share of $3.225 in a registered direct offering priced at-the-market under Nasdaq rules (Press release, Bio-Path Holdings, APR 18, 2024, View Source [SID1234642149]). Additionally, in a concurrent private placement, Bio-Path has also agreed to issue to such investors unregistered warrants to purchase up to 375,000 shares of common stock at an exercise price of $3.10 per share. The unregistered warrants to be issued in the private placement will become immediately exercisable upon issuance and will expire five years from the date of issuance. The offering is expected to close on or about April 19, 2024, subject to the satisfaction of customary closing conditions.

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Immediately prior to the registered direct offering and the concurrent private placement, the number of outstanding shares of common stock of the Company was 1,190,306. Immediately following the closing of the registered direct offering and the concurrent private placement, the number of outstanding shares of common stock of the Company will be 1,565,306.

H.C. Wainwright & Co., LLC is acting as the exclusive placement agent for the offering.

The gross proceeds to Bio-Path from the offering are expected to be approximately $1.2 million, before deducting the placement agent’s fees and other offering expenses payable by Bio-Path. BioPath currently intends to use the net proceeds from the offering for working capital and general corporate purposes.

The shares of common stock (or common stock equivalents) offered in the registered direct offering (but excluding the unregistered warrants or the shares of common stock underlying such unregistered warrants) described above are being offered and sold by Bio-Path pursuant to a "shelf" registration statement on Form S-3 (Registration No. 333-265282), including a base prospectus, previously filed with the Securities and Exchange Commission ("SEC") on May 27, 2022, and declared effective by the SEC on June 14, 2022. The offering of the shares of common stock (or common stock equivalents) are being made only by means of a prospectus, including a prospectus supplement, forming a part of the effective registration statement. A final prospectus supplement and an accompanying base prospectus relating to, and describing the terms of, the registered direct offering will be filed with the SEC and will be available on the SEC’s website located at View Source Electronic copies of the prospectus supplement and accompanying base prospectus relating to the registered direct offering, when available, may also be obtained from H.C. Wainwright & Co., LLC at 430 Park Ave., New York, New York 10022, by telephone at (212) 856-5711, or by email at [email protected].

The offer and sale of the unregistered warrants are being made in a transaction not involving a public offering and have not been registered under Section 4(a)(2) of the Securities Act of 1933, as amended (the "Securities Act") and/or Rule 506(b) of Regulation D promulgated thereunder and, along with the shares of common stock underlying such unregistered warrants, have not been registered under the Securities Act or applicable state securities laws. Accordingly, the unregistered warrants and the underlying shares of common stock may not be reoffered or resold in the United States except pursuant to an effective registration statement or an applicable exemption from the registration requirements of the Securities Act and such applicable state securities laws.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such jurisdiction.

On April 18, 2024 Bio-Path Holdings, Inc., (NASDAQ: BPTH) a biotechnology company leveraging its proprietary DNAbilize antisense RNAi nanoparticle technology to develop a portfolio of targeted nucleic acid cancer drugs, reported completion of the second dose cohort of the dose escalation portion of its Phase 1/1b clinical trial of BP1002 evaluating the ability of BP1002 to treat refractory/relapsed acute myeloid leukemia (AML) patients, including venetoclax-resistant patients (Press release, Bio-Path Holdings, APR 18, 2024, View Source [SID1234642148]).

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"We are delighted to safely progress through the second, higher dose cohort to reach an important study milestone for the United States Food and Drug Administration (FDA) to review patient study data," said Peter Nielsen, President and Chief Executive Officer of Bio-Path Holdings. "Enrollment rates have been good, and we look forward to advancing this study in even higher doses with the hope that we can sooner reach the combination therapy segment of our Phase 1/1b study with increased levels of BP1002 for the treatment of these vulnerable patients with few, if any, treatment options."

BP1002 targets the protein Bcl-2, which is responsible for driving cell survival in up to 60% of all cancers. The current standard of care for patients with AML not eligible for intensive chemotherapy is venetoclax, an oral Bcl-2 inhibitor that targets the BH3 domain of the Bcl-2 protein, in combination with a hypomethylating agent or with low-dose cytarabine. However, many patients become resistant to venetoclax treatment. A published study found that AML patients who had relapsed from frontline venetoclax-based treatment were refractory to salvage therapy and had a median survival of less than 3 months. By targeting Bcl-2 at the mRNA level rather than the protein, BP1002 may overcome and prevent some of the mechanisms of resistance that affect venetoclax treatment. Published preclinical Bio-Path studies have shown BP1002 to be a potent inhibitor against the Bcl-2 target, and we believe that its benign safety profile should enable effective BP1002 combination therapy with approved agents, such as decitabine.

The Phase 1/1b clinical trial is being conducted at several leading cancer centers in the United States, including the Weill Medical College of Cornell University, The University of Texas MD Anderson Cancer Center, Scripps Health, and The University of California at Los Angeles Cancer Center. Initially, the dose escalation portion of the clinical plan calls for a total of six evaluable patients to be treated with BP1002 monotherapy over two dose levels in a standard 3+3 design, with a starting dose of 20 mg/m2 and the second dose of 40 mg/m2. The testing of these two dose levels is now complete and the clinical trial will pause for a brief data review by the FDA, and then we expect that dose testing will continue at the next planned higher dose of 60 mg/m2. The approved treatment cycle is two doses per week over four weeks, resulting in eight doses administered over twenty-eight days. The Phase 1b portion of the study is expected to commence after completion of BP1002 monotherapy cohorts and will assess the safety and efficacy of BP1002 in combination with decitabine in refractory/relapsed AML patients.

Gail J. Roboz, M.D., is the National Principal Investigator for the Phase 1/1b trial. Dr. Roboz is a professor of medicine and director of the Clinical and Translational Leukemia Program at the Weill Medical College of Cornell University and the New York-Presbyterian Hospital in New York City. Gary Schiller, M.D., The University of California at Los Angeles Cancer Center, Maro Ohanian, D.O., Department of Leukemia, University of Texas MD Anderson Cancer Center, and David Hermel, M.D., Scripps Health, are each serving as principal investigators.

On April 18, 2024 Outrun Therapeutics ("Outrun"), the E3 ligase inhibitor and protein stabilisation specialist, reported the company exits from stealth following a $10m seed financing round (Press release, Outrun Therapeutics, APR 18, 2024, View Source [SID1234642144]). Outrun’s platform has enabled it to rapidly build a pipeline of highly selective, small molecule, first-in-class E3 ligase inhibitors, as well as identify novel E3 ligase targets across multiple disease areas. Outrun’s lead programme is focused on hard-to-treat solid tumours.

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E3 ligase inhibition in protein stabilisation is of very high interest as a therapeutic approach to treating many diseases. Cells have evolved highly sophisticated ways of keeping disease at bay, and empowering the body to take care of itself is potentially the most effective way of suppressing disease. Inhibiting targeted E3 ligases enables protein stabilisation "at source", being directly part of the tagging mechanism involved in healthy cellular processing of destabilised, unwanted, or mis-formed proteins. This restores the body’s sophisticated natural disease suppression processes and could be applicable to a wide range of indications, including oncology and neurology.

Selective protein stabilisation by inhibiting specific E3 ligases will expand the disease indications that can be addressed with protein stabilisation and minimise side effects. There are ~700 E3 ligases representing the vast number of discrete cellular processes they control, providing potential targets for Outrun to develop effective precision medicines against.

Outrun has developed a proprietary, high throughput platform which allows robust, highly accurate, quantitative assessment of the specificity and selectivity of E3 ligase targets, thereby dramatically reducing the discovery time for E3 ligase inhibitors, improving specificity and target binding. Furthermore, the platform uses engineered protein sensors (EPS) to uncover the detailed biochemistry of E3 ligases, enabling discovery of drugs with potentially superior binding, specificity, and activity. Outrun’s approach is a scalable and modular strategy for developing next-generation small molecule drugs targeting E3 ligases, particularly inhibitors that stabilise proteins.

Dr Carolyn Porter, Chief Executive Officer of Outrun Therapeutics, said: "Protein stabilisation is the mirror image of protein degradation and seeks to maintain the levels of critical proteins that are otherwise unbalanced in certain diseases, disrupting the body’s highly sophisticated natural disease suppression processes. We are bringing our world class knowledge of E3 ligase biology and protein-to-protein interactions, combined with our proprietary discovery platform, to unlock the potential of this exciting new therapeutic area."

Dr Jeffrey Moore, President at MP Healthcare Venture Management, commented: "We believe protein stabilisation via E3 ligase inhibition is a potentially powerful new therapeutic modality. With world leading research under the guidance of a talented management team, we are confident that Outrun has the potential to transform a variety of disease areas, such as oncology and neurology."

Dr Bauke Anninga, Investment Director at M Ventures, added: "We are delighted to be one of the founding investors of Outrun. The Company’s novel platform enabling rapid assessment of the specificity and selectivity of E3 ligase inhibitors, provides a highly competitive edge to reduce discovery timelines and build a first in class pipeline."

Led by a seasoned management team and a strong Board, Outrun was spun out of founder Prof. Satpal Virdee’s world-renowned MRC Protein Phosphorylation and Ubiquitylation Unit at the University of Dundee. Outrun’s Scientific Advisory Board consists of highly relevant, world-leading experts in ubiquitylation and oncology. Outrun is backed by leading venture capital investors M Ventures and MP Healthcare Venture Management.

On April 17, 2024, ImmuneOnco Biopharmaceuticals (Shanghai) Inc. (referred to as " ImmuneOnco "), HKEX stock code: 01541.HK) reported that the Phase III clinical study protocol of Timdarpacept (R&D number: IMM01) combined with Tirellizumab for PD-1/PD-L1 inhibitor failed Classic Hodgkin lymphoma (cHL) was approved by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (Press release, ImmuneOnco Biopharma, APR 17, 2024, View Source [SID1234655699]).

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IMM01 is the first SIRP-α-FC fusion protein to enter the clinical stage in China and is being developed to use in combination with other drugs to treat a variety of blood and solid tumors. Recently, the results of two Phase II clinical innovation studies in IMM01 were included in the oral report of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual meeting in 2024 (respectively, IMM01 combined with Tirellizumab in the treatment of cHL indications after previous PD-1 antibody treatment failed, and IMM01 combined with azacitide in the treatment of high-risk MDS indications for initial treatment).

In December 2023, the results of three Phase II clinical innovation studies on IMM01 were selected for oral presentation and poster presentation at the 2023 annual meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper), among which two studies were selected for oral presentation in 2023 ASH (Free ASH Whitepaper) (cHL indication and 1-line MDS indication after PD-(L)1 antibody treatment failure). The results of another 1-line CMML indication study were presented in poster form. This is the clinical research progress of IMM01 project selected for ASH (Free ASH Whitepaper) annual meeting for two consecutive years.

Updated data were reported at the ASH (Free ASH Whitepaper) meeting in 2023: The ORR, CR, and DCR of cHL patients treated with IMM01 combined with Tirelizumab after previous PD-(L)1 antibody treatment failure reached 65.2%, 17.4%, and 100%, which shown to benefit from the combination therapy in each subgroup analysis. In addition, IMM01 combined with tirellizumab was well tolerated, and no patients had permanent discontinuation due to drug-related adverse reactions. The Phase II update results received an oral presentation at ASCO (Free ASCO Whitepaper) 2024 and will be presented in Chicago on June 2.

Founder and chairman of ImmuneOnco Dr. Tian, Wenzhi said: "We are very pleased to have received CDE approval for our Phase III registered clinical study protocol for Timdarpacept (IMM01) in combination with Tirellizumab for PD-1/PD-L1 inhibitor failed Classical Hodgkin lymphoma (cHL). Clinical treatment for PD-1/PD-L1 inhibitor treatment failed cHL is an unmet clinical need especially for those patients whose onset age is relatively young. We believe that Timdarpacept through activating macrophages can turn "cold tumors" into "hot tumors", and can induce more tumor-specific T cell responses by presenting tumor antigens to T lymphocytes, thereby restoring and expanding the sensitivity and therapeutic response of patients to tirellizumab. Our scientific judgment is well supported by the obtained clinical data. In contrast, PD-1 antibody combined with another T cell-associated immune checkpoint antibody is difficult to achieve such clinical manifestations. We firmly believe that the development of Timdarpacept in combination with Tirellizumab against PD-1/PD-L1 monoclonal antibody refractory cHL will have great market competitiveness. We will quickly advance the Phase III registered clinical trial study, and strive to bring benefits to cHL patients as soon as possible."

Chief Medical Officer/Senior Vice President, ImmuneOnco Dr. Lu, Qiying said: "Today’s CDE approval of IMM01 in combination with Tirellizumab for a refractory cHL indication is an extremely important milestone for our company. The results of two clinical phase II studies on IMM01 products were all recognized and affirmed by ASCO (Free ASCO Whitepaper) in 2024, and two were accepted as oral reports. In terms of clinical development layout of IMM01 products, we have carried out a differentiated layout. Aiming at the unmet medical demand of cHL after the failure of previous PD-1/PD-L1 antibody treatment, our combined treatment mode can overcome the drug resistance of previous PD-1/PD-L1 antibody treatment, and reflects the advantages of chemotherapy treatment. It can avoid the long-term toxicity caused by chemotherapy drugs and bring long-term quality of life advantages to patients. In addition, the current efficacy data has been further improved compared to the ASH (Free ASH Whitepaper) abstract submitted in July last year, with better efficacy response (ORR/CR) for the cHL indication. Today, the phase III clinical registration study was approved by CDE indicating that the clinical development of IMM01 has fully entered the registration study stage, and this is the world’s first macromolecule drug to develop cHL registration indications against CD47 targets. At present, our team is well prepared to start the trial. We look forward to rapidly advancing the clinical development of IMM01 products, bringing new therapeutic options to the treatment of cancer patients and addressing unmet clinical needs."