On December 27, 2024 Daiichi Sankyo reported that (TSE:4568) DATROWAY (datopotamab deruxtecan) has been approved in Japan for the treatment of adult patients with hormone receptor (HR) positive, HER2 negative (IHC 0, IHC 1+ or IHC 2+/ISH-) unresectable or recurrent breast cancer after prior chemotherapy (Press release, Daiichi Sankyo, DEC 27, 2024, View Source [SID1234649334]).

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In Japan, breast cancer is the most common cancer in women.1 Approximately 92,000 cases of breast cancer were diagnosed in Japan in 2022, with approximately 17,600 deaths.1 It is estimated that 70% of diagnosed cases are considered what has been historically called HR positive, HER2 negative breast cancer (measured as HER2 score of IHC 0, IHC 1+ or IHC 2+/ISH-).

DATROWAY is the first ever TROP-2 directed medicine to be approved in Japan for HR positive, HER2 negative breast cancer and is the second DXd antibody drug conjugate (ADC) approved based on Daiichi Sankyo’s DXd ADC Technology.

The approval of DATROWAY by the Japan Ministry of Health, Labour and Welfare (MHLW) is based on results from the TROPION-Breast01 phase 3 trial. In this trial, DATROWAY significantly reduced the risk of disease progression or death by 37% compared to investigator’s choice of chemotherapy (hazard ratio [HR]=0.63, 95% confidence interval [CI]: 0.52-0.76; p<0.0001) in patients with HR positive, HER2 negative metastatic breast cancer as assessed by blinded independent central review (BICR). Median progression-free survival (PFS) was 6.9 months in patients treated with DATROWAY compared to 4.9 months in those treated with chemotherapy.

"This first global approval of DATROWAY provides patients in Japan with metastatic HR positive, HER2 negative breast cancer a new alternative to conventional chemotherapy, which is often associated with poor response rates," said Wataru Takasaki, PhD, Senior Advisor, Daiichi Sankyo. "DATROWAY also is the second DXd antibody drug conjugate approved in Japan based on technology invented by Daiichi Sankyo, emphasizing our commitment to creating new, innovative standards of care for patients with cancer."

In TROPION-Breast01, adverse reactions occurred in 93.6% (337/360 patients) of the 360 patients (including 31 Japanese patients) in the DATROWAY (6 mg/kg) arm. The most common adverse reactions included nausea (51.1%), stomatitis (50.0%), alopecia (36.4%), fatigue (23.6%), and dry eye (21.7%). In Japanese patients, interstitial lung disease (ILD) occurred in 6.5% of patients treated with DATROWAY.

DATROWAY is approved in Japan with a Warning for ILD. As cases of ILD, including fatal cases, have occurred in DATROWAY-treated patients. DATROWAY is to be used in close collaboration with a respiratory disease expert. Patients should be closely observed during therapy by monitoring for early signs or symptoms of ILD (such as dyspnea, cough or fever) and performing periodical percutaneous oxygen saturation (SpO2) tests, chest X-ray scans and chest CT scans. If abnormalities are observed, discontinue administration of DATROWAY and take appropriate measures, such as corticosteroid administration. Prior to initiation of DATROWAY therapy, a chest CT scan should be performed and medical history taken to confirm the absence of any comorbidity or history of ILD with the patient and carefully consider the eligibility of the patient for DATROWAY therapy.

Additional regulatory submissions for DATROWAY in breast cancer are under review in the EU, China, U.S. and other regions.

About TROPION-Breast01

TROPION-Breast01 is a global, randomized, multicenter, open-label phase 3 trial evaluating the efficacy and safety of intravenous DATROWAY (6 mg/kg) once per 21-day cycle versus investigator’s choice of singleagent chemotherapy (eribulin, capecitabine, vinorelbine or gemcitabine) in adult patients with unresectable or metastatic HR positive, HER2 negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who progressed on and are not suitable for endocrine therapy per investigator assessment and have received at least one additional systemic therapy for unresectable or metastatic disease.

Following disease progression or discontinuation of DATROWAY or chemotherapy, patients had the option to receive subsequent treatment at the discretion of their physician. Crossover between trial arms was not permitted.

The dual primary endpoints of TROPION-Breast01 are PFS as assessed by BICR and overall survival. Key secondary endpoints include overall response rate, duration of response, investigator-assessed PFS, disease control rate, time to first subsequent therapy and safety. The PFS data and additional results for key secondary endpoints of TROPION-Breast01 were published in the Journal of Clinical Oncology.

TROPION-Breast01 enrolled 732 patients in Africa, Asia, Europe, North America and South America. For more information visit ClinicalTrials.gov.

About Hormone Receptor Positive, HER2 Negative Breast Cancer
Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide.3 More than two million breast cancer cases were diagnosed in 2022 with more than 665,000 deaths globally.3 In Japan, breast cancer is the most common cancer in women, with approximately 92,000 cases of breast cancer diagnosed in 2022.1 While survival rates are high for those diagnosed with early breast cancer, only about 30% of patients diagnosed with or who progress to metastatic disease are expected to live five years following diagnosis.

Approximately 70% of diagnosed cases are considered what has been historically called HR positive, HER2 negative breast cancer (measured as HER2 score of IHC 0, IHC 1+ or IHC 2+/ISH-).2 Endocrine therapies are widely given consecutively in the early lines of treatment for HR positive metastatic breast cancer. 4 However, after initial treatment, further efficacy from endocrine therapy is often limited. 4 The current standard of care following endocrine therapy is chemotherapy, which is associated with poor response rates and outcomes.

About DATROWAY
DATROWAY (datopotamab deruxtecan) is a TROP-2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, DATROWAY is one of six DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programs in AstraZeneca’s ADC scientific platform. DATROWAY is comprised of a humanized anti-TROP-2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

DATROWAY (6 mg/kg) is approved in Japan for the treatment of adult patients with HR positive, HER2 negative (IHC 0, IHC 1+ or IHC 2+/ISH-) unresectable or recurrent breast cancer after prior chemotherapy based on results from the TROPION-Breast01 trial.

About the DATROWAY Clinical Development Program
A comprehensive global clinical development program is underway with more than 20 trials evaluating the efficacy and safety of DATROWAY across multiple cancers, including non-small cell lung cancer, triple negative breast cancer, and HR positive, HER2 low or negative breast cancer. The program includes seven phase 3 trials in lung cancer and five phase 3 trials in breast cancer evaluating DATROWAY as a monotherapy and in combination with other anticancer treatments in various settings.

On December 27, 2024 Vor Bio (Nasdaq: VOR), a clinical-stage cell and genome engineering company, reported that it has entered into a securities purchase agreement for a private investment in public equity financing (the PIPE) that is expected to result in gross proceeds of approximately $55.6 million, before deducting placement agent fees and other expenses (Press release, Vor BioPharma, DEC 27, 2024, View Source [SID1234649333]).

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Pursuant to the terms of the securities purchase agreement, at the closing of the PIPE, Vor Bio will issue an aggregate of 55,871,260 shares of common stock and accompanying warrants to purchase an aggregate of 69,839,075 shares of common stock at a combined price of $0.99425 per share and accompanying warrants. The warrants will have a per share exercise price of $0.838 and may be exercised at any time on or after the closing date and through the seventh anniversary of the closing date. The combined price per share and accompanying warrant was based in part upon the last reported sale price of the common stock on the Nasdaq Global Select Market. If exercised for cash, the warrants would result in additional gross proceeds to Vor Bio of up to approximately $58.5 million.

The PIPE was led by new investor, Reid Hoffman, and included participation from existing investor and Vor Bio’s largest stockholder, RA Capital Management. In addition, as part of the PIPE, each of Mr. Hoffman, or his duly appointed nominee, and RA Capital Management are being granted one board seat and one board observer seat.

"Acute myeloid leukemia ranks among the deadliest cancers in the world, and a treatment for it has been sought for decades," said Mr. Hoffman. "The history of this illness has had a few dramatic breakthroughs but also many, many failures. Vor’s trem-cel therapy, which uses CRISPR/cas9 to edit the bone marrow of patients, represents a new potential breakthrough. Early data released by Vor suggest a potent effect, which now must be confirmed by future trials. I am delighted to support this company that uses a game-changing technology that will hopefully impact the lives of patients with this lethal cancer – but even more the trajectory of cancer therapy in general."

Stifel is acting as sole placement agent for the PIPE.

Vor Bio expects to use net proceeds from the PIPE to fund clinical and preclinical development of its pipeline candidates and for general corporate purposes. The PIPE is expected to close on December 30, 2024, subject to the satisfaction of customary closing conditions.

Vor Bio expects to announce updated clinical data from the Phase 1/2 VBP301 trial of VCAR33ALLO in the first half of 2025 and updated clinical data from the Phase 1/2a VBP101 trial of trem-cel in combination with Mylotarg in the second half of 2025.

The securities being issued and sold in the PIPE have not been registered under the Securities Act of 1933, as amended (the Securities Act). Accordingly, these securities may not be offered or sold in the United States, except pursuant to an effective registration statement or an applicable exemption from the registration requirements of the Securities Act. Concurrently with the execution of the securities purchase agreement, Vor Bio and the investors entered into a registration rights agreement pursuant to which Vor Bio has agreed to file a registration statement with the Securities and Exchange Commission registering the resale of the shares of common stock and the shares of common stock issuable upon the exercise of warrants issued in the PIPE.

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 state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.

On December 27, 2024 Vincerx Pharma, Inc. (Nasdaq: VINC), a biopharmaceutical company aspiring to address the unmet medical needs of patients with cancer through paradigm-shifting therapeutics, reported that it has entered into a binding term sheet for a proposed merger with Oqory, Inc., a privately-held, clinical-stage company developing ADCs for the treatment of multiple oncology indications (Press release, Vincerx Pharma, DEC 27, 2024, View Source [SID1234649332]).

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Upon completion of the proposed merger, Oqory, Inc. will merge with Vincerx Pharma, Inc. Post-closing, Oqory equity holders are expected to own approximately 95% of the combined entity, while Vincerx equity holders will hold about 5%. The transaction includes a minimum fully diluted equity value of $13.66 million for existing Vincerx stockholders at closing and, as a condition to the closing of the merger, completion of a concurrent offering of Vincerx equity securities of at least $20 million. Additionally, Oqory-designated investors will provide interim financing to Vincerx of $1.5 million in two tranches, approximately $1,000,000 of which was funded today through the issuance of common stock and pre-funded warrants along with accompanying common stock warrants and approximately $500,000 of which will be funded on or prior to January 31, 2025. The merger is subject to customary closing conditions, including due diligence, regulatory approvals, negotiation of a definitive merger agreement, stockholder approval from both parties, completion of the minimum $20 million financing, and the continued listing of Vincerx’s common stock on Nasdaq.

Vincerx is also implementing additional streamlining and cost-control measures, including a workforce reduction, as it pursues due diligence and transaction-related work. As part of this workforce reduction, Dr. Ahmed Hamdy, Chairman and Chief Executive Officer (CEO), has stepped down as CEO but will remain as Chairman. Dr. Raquel Izumi has stepped down as President and Chief Operations Officer and taken over as Acting CEO in a consulting capacity. Alexander Seelenberger has stepped down as Chief Financial Officer, and Kevin Hass, the Company’s Vice President and Controller, has taken over as Acting Chief Financial Officer. Mr. Seelenberger has agreed to provide ongoing assistance in a consulting capacity to assist the Company as it pursues its strategic efforts.

"This strategic transaction highlights Vincerx’s commitment to develop ADCs with improved safety profiles that allow patients to thrive on—rather than endure—their cancer therapies," said Raquel Izumi, Ph.D., Acting Chief Executive Officer. "Oqory’s anti-TROP2 ADC has shown favorable efficacy and safety in the clinic. Among approximately 150 treated patients, results include an 83% overall response rate and 100% disease control rate in first-line triple-negative breast cancer (TNBC; n=30). Unlike other TROP2 ADCs in Phase 3, no cases of interstitial lung disease or Grade 3 and above stomatitis have been reported. Oqory’s Phase 3 studies of OQY-3258 are ongoing to confirm these promising findings."

About OQY-3258 (also known as ESG401)
OQY-3258 is Oqory’s anti-TROP2 ADC with an optimized enzyme-dependent linker technology and an SN-38 payload with established efficacy and manageable side effect profile. OQY-3258 has completed Phase 1/2 development in over 150 patients with solid tumors, including metastatic HR+/HER2- and triple-negative breast cancer. OQY-3258 has shown efficacy in these patients, including reduction of brain metastasis and responses in heavily pretreated patients. To date, OQY-3258 has exhibited a differentiated safety profile vs. Trodelvy and other TROP2 ADCs in Phase 3 development. Notably, no interstitial lung disease or ocular surface events have been observed. Gastrointestinal effects have been mild and mainly Grade 1/2. Neutropenia and leukopenia have been the major AEs, which were manageable and did not result in discontinuation of study drug. OQY-3258 is being evaluated in a Phase 3 study as first-line treatment in patients with unresectable recurrent or metastatic triple-negative breast cancer (NCT06732323) and in a Phase 3 study in patients with unresectable locally advanced or metastatic HR+/HER2- breast cancer (NCT06383767).

On December 27, 2024 Phio Pharmaceuticals Corp. (Nasdaq: PHIO), a clinical-stage biotechnology company that develops therapeutics using its INTASYL siRNA gene silencing technology to make the body’s immune cells more effective in killing cancer cells, reported that it has entered into definitive agreements for the purchase and sale of an aggregate of 240,000 shares of its common stock at a purchase price of $2.00 per share in a registered direct offering priced at-the-market under Nasdaq rules (Press release, Phio Pharmaceuticals, DEC 27, 2024, View Source [SID1234649331]). In addition, in a concurrent private placement, the Company will issue unregistered warrants to purchase up to 240,000 shares of common stock. The warrants will have an exercise price of $2.00 per share, will be exercisable upon issuance and expire five years following the date of issuance. The closing of the offering is expected to occur on or about December 24, 2024, subject to the satisfaction of customary closing conditions.

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

The aggregate gross proceeds to the Company from the offering are expected to be $0.48 million, before deducting the placement agent fees and other offering expenses payable by the Company. The Company currently intends to use the net proceeds from the offering for working capital and other general corporate purposes.

The shares of common stock (but not the warrants issued in the private placement or the shares of common stock underlying such warrants) are being offered by the Company pursuant to a "shelf" registration statement on Form S-3 (File No. 333-279557) filed with the Securities and Exchange Commission ("SEC") on May 20, 2024 and became effective on July 1, 2024. The registered direct offering of the shares of common stock is being made only by means of a prospectus, including a prospectus supplement, forming a part of the effective registration statement. The prospectus supplement and the accompanying prospectus relating to the shares of common stock being offered in the registered direct offering will be filed with the SEC and be available at the SEC’s website at www.sec.gov. Electronic copies of the prospectus supplement and the accompanying prospectus relating to the registered direct offering may also be obtained, when available, by contacting H.C. Wainwright & Co., LLC at 430 Park Avenue, 3rd Floor, New York, NY 10022, by telephone at (212) 856-5711 or e-mail at [email protected].

The warrants described above are being issued in a concurrent private placement under Section 4(a)(2) of the Securities Act of 1933, as amended (the "Securities Act"), and Regulation D promulgated thereunder and, along with the shares of common stock underlying the warrants, have not been registered under the Securities Act, or applicable state securities laws. Accordingly, the warrants and underlying shares of common stock may not be offered or sold 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 any of the securities described herein, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or jurisdiction.

On December 27, 2024 Outlook Therapeutics, Inc. (Nasdaq: OTLK), a biopharmaceutical company that achieved regulatory approval in the European Union and the United Kingdom earlier this year for the first authorized use of an ophthalmic formulation of bevacizumab for the treatment of wet age-related macular degeneration (wet AMD), reported financial results for fiscal year 2024 and provided a corporate update (Press release, Outlook Therapeutics, DEC 27, 2024, View Source [SID1234649330]).

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"Over the course of the past year, our team has continued to execute and progress the development of ONS-5010/LYTENAVA in Europe and the United States. Following the receipt of our first positive reimbursement decision worldwide for LYTENAVA from NICE in the United Kingdom, our team continues to make preparations for commercial launch in the UK and Germany, which is expected in the first half of calendar 2025," commented Lawrence Kenyon, Chief Financial Officer and Interim Chief Executive Officer of Outlook Therapeutics. "We expect to receive the month 3 NORSE EIGHT efficacy data in January 2025 and are continuing preparations for the planned resubmission of our BLA in the first quarter of calendar 2025. We believe that 2025 holds significant opportunity for Outlook Therapeutics and we remain confident in the potential of ONS-5010/LYTENAVA to provide a meaningful impact globally for the treatment of wet AMD."

Upcoming Anticipated Milestones

Final efficacy data from NORSE EIGHT expected in January 2025;
Resubmission of the ONS-5010 BLA targeted for Q1 CY2025;
Initial commercial launches in Europe planned to commence in first half of CY2025; and
Potential for US FDA approval of ONS-5010 in second half of CY2025.
ONS-5010 / LYTENAVA (bevacizumab-vikg) Clinical and Regulatory Update

In May 2024, the European Commission granted Marketing Authorization for LYTENAVA (bevacizumab gamma) for the treatment of wet AMD in the EU. Additionally, in July 2024, the UK Medicines and Healthcare products Regulatory Agency (MHRA) granted Marketing Authorization for LYTENAVA (bevacizumab gamma) for the same indication in the UK. In December 2024, the National Institute for Health and Care Excellence (NICE) recommended LYTENAVA (bevacizumab gamma) as an option for the treatment of wet AMD. Plans for a potential 2025 launch in the UK and Germany are ongoing. Outlook Therapeutics remains confident that ONS-5010/ LYTENAVA is an important therapy for the treatment of wet AMD in place of off-label repackaged bevacizumab that has not received regulatory approval for use in retina diseases such as wet AMD.

Previously, the Company reported that in the NORSE EIGHT trial, ONS-5010 did not meet the pre-specified non-inferiority endpoint at week 8 set forth in the special protocol assessment (SPA) with the U.S. Food and Drug Administration (FDA). However, the preliminary data from the trial demonstrated an improvement in vision and the presence of biologic activity, as well as a continued favorable safety profile for ONS-5010. Analysis of the data is ongoing as the month 3 data from NORSE EIGHT is being collected, which is expected to be available in January 2025. Upon receipt of the full month 3 efficacy and safety results for NORSE EIGHT, Outlook Therapeutics plans to resubmit the BLA for ONS-5010 in the first quarter of calendar 2025.

LYTENAVA (bevacizumab gamma) is the first and only authorized ophthalmic formulation of bevacizumab for use in treating wet AMD in adults in the EU and UK and has an initial 10 years of market exclusivity. Authorization may also be sought in other European countries, Japan, and elsewhere. As part of a multi-year planning process, Outlook Therapeutics entered into a strategic collaboration with Cencora (formerly AmerisourceBergen) to support the commercial launch of LYTENAVA globally following regulatory approvals. The collaboration and integrated approach is designed to support market access and efficient distribution of LYTENAVA to benefit all stakeholders, including retina specialists, providers and patients.

In the EU and the UK and other regions outside of the US, Outlook Therapeutics is planning to commercialize LYTENAVA (bevacizumab gamma) directly and is also assessing potential licensing and partnering options. Additionally, if approved by the FDA, Outlook Therapeutics plans to commercialize ONS-5010/LYTENAVA (bevacizumab-vikg) directly in the US.

Financial Highlights for the 2024 Fiscal Year Ended September 30, 2024

For the fiscal year ended September 30, 2024, Outlook Therapeutics reported a net loss of $75.4 million, or $4.06 per basic and diluted share, compared to a net loss of $59.0 million, or $4.72 per basic and diluted share, for the prior fiscal year.

As of September 30, 2024, Outlook Therapeutics had cash and cash equivalents of $14.9 million.

About ONS-5010 / LYTENAVA (bevacizumab-vikg, bevacizumab gamma)

ONS-5010/LYTENAVA is an ophthalmic formulation of bevacizumab for the treatment of wet AMD. LYTENAVA (bevacizumab gamma) is the subject of a centralized Marketing Authorization granted by the European Commission in the European Union (EU) and Marketing Authorization granted by the Medicines and Healthcare products Regulatory Agency (MHRA) in the United Kingdom (UK) for the treatment of wet age-related macular degeneration (wet AMD).

In the United States, ONS-5010/LYTENAVA (bevacizumab-vikg) is investigational and is being evaluated in an ongoing non-inferiority study for the treatment of wet AMD.

Bevacizumab-vikg (bevacizumab gamma in the EU and UK) is a recombinant humanized monoclonal antibody (mAb) that selectively binds with high affinity to all isoforms of human vascular endothelial growth factor (VEGF) and neutralizes VEGF’s biologic activity through a steric blocking of the binding of VEGF to its receptors Flt-1 (VEGFR-1) and KDR (VEGFR-2) on the surface of endothelial cells. Following intravitreal injection, the binding of bevacizumab to VEGF prevents the interaction of VEGF with its receptors on the surface of endothelial cells, reducing endothelial cell proliferation, vascular leakage, and new blood vessel formation in the retina.