On July 3, 2023 Abeona Therapeutics Inc. (Nasdaq: ABEO) reported that it has raised $25 million at-the-market from select existing investors, primarily to fund initiation of the Company’s launch preparations in anticipation of the EB-101 Biologics License Application (BLA) submission and potential approval (Press release, Abeona Therapeutics, JUL 3, 2023, View Source [SID1234633027]).

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!

The company has entered into definitive agreements with certain existing institutional investors for the issuance and sale of 3,284,407 shares of its common stock, and in lieu of common stock, pre-funded warrants to purchase 2,919,140 shares of its common stock at an offering price of $4.03 per share (or $4.0299 per pre-funded warrant, which represents the per share offering price for the common stock less the $0.0001 per share exercise price for each pre-funded warrant). The pre-funded warrants will be immediately exercisable at a nominal exercise price of $0.0001 per share and may be exercised at any time until the pre-funded warrants are exercised in full. The closing of the offering is expected to occur on or about July 6, 2023, subject to the satisfaction of customary closing conditions.

The offering was led by Nantahala Capital Management, LLC and included participation by Adage Capital Partners LP and two other existing institutional investors.

Cantor Fitzgerald & Co. is acting as the sole lead-placement agent for the offering. A.G.P./Alliance Global Partners is acting as the co-placement agent for the offering.

The gross proceeds to Abeona from this offering are expected to be approximately $25 million, before deducting the placement agent’s fees and other offering expenses. Abeona intends to use the net proceeds from the offering primarily to fund preparations for commercialization of its product candidate EB-101, as well as for working capital and general corporate purposes. Based on EB-101’s Rare Pediatric Disease designation, Abeona expects to qualify to receive a priority review voucher (PRV) upon BLA approval and subject to final determination by the FDA. The PRV can be used to receive an expedited review process of a subsequent marketing application for a different product or sold to another company to create additional capital to fund the EB-101 launch.

The securities described above are being offered pursuant to a shelf registration statement on Form S-3 (File No. 333-256850) that was filed with the Securities and Exchange Commission (the "SEC") on June 7, 2021 and amended on August 27, 2021 and October 19, 2021, and was declared effective by the SEC on October 22, 2021. The offering is being made only by means of the written prospectus and prospectus supplement that form a part of the registration statement. The prospectus supplement and the accompanying prospectus that form a part of the registration statement have been filed with the SEC and are available on the SEC’s website at www.sec.gov. Copies of the prospectus supplement and the accompanying prospectus may also be obtained by contacting Cantor Fitzgerald & Co., Attention: Equity Capital Markets, 499 Park Avenue, 4th Floor, New York, NY 10022, or by e-mail at [email protected].

On July 3, 2023 Astrazeneca reported positive high-level results from the TROPION-Lung01 Phase III trial showed datopotamab deruxtecan (Dato-DXd) demonstrated a statistically significant improvement for the dual primary endpoint of progression-free survival (PFS) compared to docetaxel, the current standard of care chemotherapy, in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) treated with at least one prior therapy (Press release, AstraZeneca, JUL 3, 2023, View Source [SID1234633020]).

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!

For the dual primary endpoint of overall survival (OS), the data were not mature and an early trend was observed in favour of datopotamab deruxtecan versus docetaxel that did not meet the prespecified threshold for statistical significance at this interim analysis. The trial will continue as planned to assess OS with greater maturity. The investigators and participants will remain blinded to the results.

The safety profile of datopotamab deruxtecan was consistent with previous clinical trials with no new safety signals identified. All grade interstitial lung disease was generally consistent with prior clinical trials, with the majority being low grade. Some Grade 5 events were observed.

Datopotamab deruxtecan is a specifically engineered TROP2-directed DXd antibody drug conjugate (ADC) being jointly developed by AstraZeneca and Daiichi Sankyo.

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "With TROPION-Lung01, we met the dual primary endpoint of progression-free survival, challenging the entrenched standard of care in a previously treated and unselected patient population that has long deserved an alternative to chemotherapy. These first Phase III trial results from the datopotamab deruxtecan clinical programme provide compelling evidence for the potential role this TROP2-directed antibody drug conjugate can play in treating patients with lung cancer."

Ken Takeshita, MD, Global Head, Oncology R&D, Daiichi Sankyo, said: "We are encouraged by the statistically significant results of the dual primary endpoint of progression-free survival seen with datopotamab deruxtecan and look forward to the final overall survival analysis. We plan to share these data with regulatory authorities to discuss next steps."

More than one million people worldwide are diagnosed with advanced NSCLC each year.1,2 While immunotherapy and targeted therapies have improved outcomes in the 1st-line metastatic setting, most patients eventually experience disease progression and receive chemotherapy.3-5 For decades, chemotherapy has been the last treatment available for patients with advanced NSCLC in the absence of other treatment options and despite limited effectiveness and known side effects.3-5 TROP2 is a protein highly expressed in a large majority of lung cancers. There are currently no TROP2-directed ADCs approved for the treatment of patients with lung cancer.6-8

TROPION-Lung01 enrolled patients with and without actionable genomic alterations, such as EGFR and ALK. Patients with actionable genomic alterations were previously treated with platinum-based chemotherapy and an approved targeted therapy. Patients without actionable genomic alterations were previously treated, concurrently or sequentially, with platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor.

The data will be presented at a forthcoming medical meeting and shared with health authorities.

Notes

Non-small cell lung cancer
More than one million people worldwide are diagnosed with advanced NSCLC each year.1,2 While immunotherapy and targeted therapies have improved outcomes in the 1st-line metastatic setting, most patients eventually experience disease progression and receive chemotherapy.3-5 For decades, chemotherapy has been the last treatment available for patients with advanced NSCLC in the absence of other treatment options and despite limited effectiveness and known side effects.3-5

TROP2 is a protein highly expressed in a large majority of lung cancers.6 There are currently no TROP2-directed ADCs approved for the treatment of patients with lung cancer.7,8

TROPION-Lung01
TROPION-Lung01 is a global, randomised, multicentre, open-label Phase III trial evaluating the efficacy and safety of datopotamab deruxtecan (6.0 mg/kg) versus docetaxel (75 mg/m2) in patients with locally advanced or metastatic NSCLC, with or without actionable genomic alterations, treated with at least one prior therapy. Patients without actionable genomic alterations were previously treated, concurrently or sequentially, with platinum-based chemotherapy and a prior PD-1 or PD-L1 inhibitor. Patients with actionable genomic alterations were previously treated with platinum-based chemotherapy and targeted therapy as approved for their detected genomic alteration.

The dual primary endpoints of TROPION-Lung01 are PFS as assessed by blinded independent central review (BICR) and OS. Key secondary endpoints include investigator-assessed PFS, objective response rate, duration of response, time to response and disease control rate as assessed by both BICR and an investigator, and safety.

TROPION-Lung01 enrolled approximately 600 patients at sites in Asia, Europe, North America and South America. For more information visit ClinicalTrials.gov.

Datopotamab deruxtecan (Dato-DXd)
Datopotamab deruxtecan (Dato-DXd) is an investigational TROP2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, datopotamab deruxtecan is one of five lead ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programmes in AstraZeneca’s ADC scientific platform. Datopotamab deruxtecan is comprised of a humanized anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads, an exatecan derivative, via tetrapeptide-based cleavable linkers.

A comprehensive development programme is underway globally with more than 12 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple TROP2-targetable tumours, including NSCLC, triple-negative breast cancer and hormone receptor-positive, HER2-low or negative breast cancer. Beyond the TROPION programme, datopotamab deruxtecan is also being evaluated in novel combinations in several ongoing trials.

In NSCLC, the TROPION-Lung07, TROPION-Lung08 and AVANZAR Phase III trials are evaluating datopotamab deruxtecan and immune checkpoint inhibitor combinations as potential 1st-line treatment options for patients with advanced or metastatic disease, a strategy informed by the results of two early trials. AstraZeneca is also researching a potential diagnostic test to help identify patients most likely to benefit from treatment with datopotamab deruxtecan.

On July 2, 2023 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, autoimmune, metabolic, ophthalmology and other major diseases, and IASO Biotechnology ("IASO Bio"), a clinical-stage biopharmaceutical company engaged in discovering, developing, and manufacturing innovative cell therapies and antibody products, reported that China’s National Medical Products Administration (NMPA) has approved the New Drug Application (NDA) for FUCASO (Equecabtagene Autoleucel, co-developed and co-commercialized by Innovent and IASO Bio, Innovent R&D code: IBI326, IASO Bio R&D code: CT103A), the first fully-human BCMA-directed chimeric antigen receptor (CAR) T cell therapy for adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least three prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent (Press release, Innovent Biologics, JUL 2, 2023, View Source [SID1234633034]).

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!

FUCASO (Equecabtagene Autoleucel) is a BCMA-directed CAR T cell therapy, using lentivirus as a gene vector to transfect autologous T cells. The CAR contains a fully-human scFv, CD8a hinge and transmembrane, and 4-1BB-mediated co-stimulation and CD3ζ activation domains. Based on rigorous selection and screening of the molecular structures, and comprehensive in vivo and in vitro evaluation, FUCASO has demonstrated rapid and potent efficacy as well as prolonged persistency in RRMM patients, providing higher and deeper responses and long-term clinical benefit.

The NDA approval was based on the results from the FUMANBA-1 clinical study (CTR20192510, NCT05066646), a multi-center Phase I/II registrational clinical trial conducted in China to evaluate the efficacy of Equecabtagene Autoleucel in patients with RRMM. In June 2023, updated data from this ongoing study was presented as a poster presentation (Abstract Number: 8025) at the 2023 Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), in which Equecabtagene Autoleucel demonstrated remarkable efficacy and favorable safety profiles.

A total of 103 subjects received a dose of 1.0×106 CAR-T cells/kg, with a median follow-up time of 13.8 (0.4, 27.2) months.

Among the 101 evaluable patients, the overall response rate (ORR) was 96%, and the stringent complete response/ complete response (sCR/CR) rate was 74.3%. Median time to response (mTTR) was only 16 days, and the 12-month PFS rate was 78.8%. 95% of the patients achieved minimal residual disease (MRD) negativity, and all sCR/CR patients achieved MRD negativity. Of the 12 patients with prior CAR-T therapy, 9 achieved CR, and 5 achieved sCR (including 4 patients that sustained sCR for over 18 months post-infusion). In 89 patients without prior CAR-T therapy, 78.7% reached sCR/CR.
Of the 103 patients, only one experienced grade ≥3 cytokine release syndrome (CRS), and 2 experienced grade 1-2 immune effector cell-associated neurotoxicity syndrome (ICANS). All patients with CRS or ICANS recovered after the treatment.
Equecabtagene Autoleucel was still detectable in 50% and 40% respectively of the patients who completed 12-month and 24-month follow-ups after infusion. Only 19.4% of the patients were anti-drug antibody (ADA)-positive after Equecabtagene Autoleucel infusion.
The Principal Investigators of FUMANBA-1 study, Prof. Lugui Qiu, MD, Chinese Academy of Medical Science Hematology Hospital, and Prof. Chunrui Li, MD, PhD, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology: "There’s a significant unmet clinical need for the treatment of multiple myeloma (MM) in China. As a fully-human BCMA CAR-T therapy, FUCASO has demonstrated remarkable efficacy, with evidence of deep and durable response for high-quality survival for MM patients. We believe that FUCASO’s approval will offers clinicians a novel breakthrough option benefiting patients with later-line RRMM."

Dr. Hui Zhou, Senior Vice President of Innovent Biologics, stated, "Multiple myeloma is a common hematology malignant disease with high incidence rate, and relapse and refractory are almost inevitable after current treatments. There’s an urgent unmet need of a treatment with well-tolerated and long persistence for RRMM patients in China. FUCASO, as an innovative fully-human BCMA-directed T cell therapy, has demonstrated robust and long-lasting efficacy and outstanding safety in long-term follow-up data from the registrational clinical study, which underscores its potential to be a pioneering treatment option for patients with RRMM. We are very pleased with the approval of FUCASO and hope it could benefit RRMM patients as the first approved BCMA CAR-T therapy in China."

Ms. Jinhua Zhang, Chairman and Chief Executive Officer of IASO Bio, stated, "We are excited that FUCASO was approved as a new drug, which is a significant milestone for our team. FUCASO is not only IASO Bio’s first commercialized product but is also the world’s first commercially available fully-human CAR-T therapy. Furthermore, FUCASO is the first self-developed and independently manufactured CAR-T cell therapy in China as well as China’s first approved BCMA CAR-T product and first approved cell therapy for the treatment of MM in China. The NMPA’s NDA approval of FUCASO will help us in achieving our strategic goal of bringing groundbreaking treatment options, as well as new hope for a potential cure, to MM patients in need."

About Multiple Myeloma (MM)
Multiple Myeloma (MM) is a blood cancer that often infiltrates the bone marrow causing anemia, kidney failure, immune problems, and bone fractures. For MM patients, common first-line drug treatments include proteasome inhibitors, immunomodulatory drugs, and alkylating agents. While treatment may result in remission, most patients will inevitably enter the relapsed or refractory stage as there’s currently no cure. As a result, there is a significant unmet need for patients with relapsed or refractory multiple myeloma. According to Frost & Sullivan, new MM cases in China rose from 20,100 in 2018 to 22,400 in 2022 and are expected to increase to 25,700 by 2027.

About FUCASO (Equecabtagene Autoleucel)
FUCASO (Equecabtagene Autoleucel) is an innovative fully-human anti- BCMA CAR-T cell therapy which uses lentivirus as a gene vector to transfect autologous T cells. The CAR contains a fully-human scFv, CD8a hinge and transmembrane, and 4-1BB-mediated co-stimulation and CD3ζ activation domains. Based on rigorous selection and screening of the molecular structures, and comprehensive in vivo and in vitro evaluation, FUCASO has demonstrated rapid and potent efficacy as well as prolonged persistency in RRMM patients. FUCASO (Equecabtagene Autoleucel) is approved by China’s NMPA for the treatment of RRMM. Innovent and IASO Bio are responsible for joint development and commercialization of FUCASO (Equecabtagene Autoleucel) for the treatment of RRMM in mainland China.

Furthermore, Equecabtagene Autoleucel received Orphan Drug Designation (ODD) designation from the U.S. Food and Drug Administration (FDA) for the treatment of RRMM and obtained the U.S. FDA IND approval. Equecabtagene Autoleucel also received Regenerative Medicine Advanced Therapy (RMAT) and Fast Track (FT) Designations in February 2023 from the FDA. In addition to multiple myeloma, the NMPA has accepted another IND application for the new extended indication of Neuromyelitis Optica Spectrum Disorder (NMOSD).

On July 1, 2023 SystImmune, Inc (SystImmune), a clinical-stage biopharmaceutical company, reported that the U.S. Food and Drug Administration (FDA) authorized the company to proceed with the planned clinical study of BL-B01D1 in the Investigational New Drug (IND) application on June 30, 2023 (Press release, SystImmune, JUL 1, 2023, View Source [SID1234633013]). This milestone paves the way for Phase 1 clinical trials of BL-B01D1 in subjects with metastatic or unresectable Non-Small Cell Lung Cancer (NSCLC) in the United States.

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!

The clearance of this IND application marks a significant milestone for SystImmune as the company continues to advance its pipeline of novel therapeutic candidates into clinical development. Dr. Yi Zhu, Chief Executive Officer of SystImmune, commented, "Our mission at SystImmune is to invent therapies that offer meaningful clinical benefit to patients, and the FDA green light of our IND application for BL-B01D1 is a testament to our commitment. Together, with all our clinical partners, trial treatment centers, and global regulatory agencies, we hope to provide significant and global contributions to the cancer treatment landscape."

"We are excited to receive FDA clearances for the IND application of Bl-B01D1, the first-in-class bi-specific ADC. This novel therapy holds tremendous promise in addressing the urgent need for improved treatment options for patients with advanced NSCLC," stated Dr. Martin S. Olivo, Chief Medical Officer at SystImmune. "Following encouraging results from clinical studies involving over 100 patients in the China-based first-in-human study, we eagerly anticipate commencing the clinical investigation of BL-B01D1 in diverse global population groups."

About BL-B01D1

BL-B01D1 is a first-in-class bispecific antibody-drug conjugate (ADC) developed by SystImmune, targeting both EGFR and HER3, proteins that are highly expressed in most epithelial tumors. The tetravalent BL-B01D1 possesses two binding domains blocking each Growth Factor Receptor, which both drive cancer cell proliferation and survival. Inheriting the SI-B001 mechanisms of action, BL-B01D1 effectively blocks EGFR and HER3 signals to cancer cells, thereby reducing proliferation and survival signals. Upon antibody-mediated internalization, BL-B01D1 is trafficked to cancer cell lysosomes and liberates its therapeutic payload that induced genotoxic stress activating pathways leading to cancer cell death.

The two targets of BL-B01D1 are broadly expressed in epithelial tumors, including NSCLC, Head and Neck Squamous Cell Carcinoma, Nasopharyngeal carcinoma, Gastrointestinal tumors, Gynecological tumors, and others. The therapeutic conjugated toxin of BL-B01D1 comprises SystImmune’s Ex-0115 linker-payload platform, a proprietary Top1 inhibitor conjugated to the bi-specific antibody by a stable, cleavable linker. Each BL-B01D1 carries 7-8 units of SystImmune’s proprietary ED-04 toxin.

Clinical studies conducted thus far have demonstrated compelling results for BL-B01D1. In subjects with EGFR-mutated NSCLC that have progressed on up to three lines of Standard of Care (SOC) treatments, BL-B01D1 achieved an overall response rate (ORR) exceeding 40%. Furthermore, in subjects with NSCLC with mutated EGFR, BL-B01D1 exhibited an ORR of over 60%. These findings were recently presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in June 2023, and the abstract of the clinical study can be accessed at the following link: BL-B01D1 ASCO (Free ASCO Whitepaper) Abstract. These results underscore the potential of BL-B01D1 as an effective treatment option for patients with different molecular profiles.

On July 1, 2023 Hamlet Pharma reported that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for Alpha1H, a highly selective synthetic peptide for treatment of non-muscle invasive bladder (NMIBC) (Press release, HAMLET Pharma, JUL 1, 2023, View Source;utm_medium=rss&utm_campaign=fda-clearance-of-ind-application-for-alpha1h-for-the-treatment-of-non-muscle-invasive-bladder-cancer [SID1234633007]). Working closely with their US based partner, Target Health LLC, a New Jersey-based, full-service CRO, the FDA’s ‘Study May Proceed’ letter begins a hopeful new chapter for the treatment of NMIBC patients globally. Studies with Alpha1H show a combination of a lack of toxicity with a high selectivity for cancerous cells, resulting in massive cell shedding in solid tumors.

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 milestone for Alpha1H underscores the urgency of our mission to bring this innovative therapy to unmet needs in the treatment of NMIBC patients. The FDA’s clearance of the Hamlet IND bolsters our plans to expand clinical research in the future for this important compound." says Catharina Svanborg, Chairman of the Board/Founder, Lead Researcher.

About the Alpha1H Clinical Program – The clinical trial, now open with the US FDA, clears the path to next phases with possible future trials in the US and other international markets.

Treatment of non-muscle-invasive bladder cancer includes transurethral resection of bladder tumor (TURBT) followed by intravesical BCG immunotherapy. Alpha1H treatment acts as an ablative-type treatment for early-stage patients and is administered during the period after diagnosis and prior to TURBT. This period is usually a non-interventional period, and Alpha1H would be considered an adjuvant treatment which could benefit patients awaiting TURBT and improve outcomes.

With no toxicity detected in studies to date, Alpha1H acts as an anti-cancer therapeutic, based on a synthetic-variant of the protein-lipid complex in human breast milk, alpha-lactalbumin and oleic acid. The alpha-lactalbumin protein, known to be essential for the survival of lactating mammals, targets and killing tumor cells with great precision, Hamlet Pharma is developing this peptide-based molecular approach as an effective cancer drug pipeline with a high degree of selectivity against a variety of cancers.