ON December 29, 2024 IDEAYA Biosciences, Inc. (NASDAQ: IDYA), a precision medicine oncology company committed to the discovery and development of targeted therapeutics, reported that it has entered into an exclusive license agreement for SHR-4849, a novel DLL3-targeting Topo-I-payload ADC program with Jiangsu Hengrui Pharmaceuticals Co., Ltd. (Hengrui Pharma, SHA: 600276), an innovative global pharmaceutical company headquartered in China focused on unmet clinical needs (Press release, Ideaya Biosciences, DEC 29, 2024, View Source [SID1234649352]). Under the terms of the agreement, IDEAYA will develop and commercialize SHR-4849 worldwide outside of Greater China.

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"There is significant unmet medical need in DLL3-expressing solid tumors, and we are excited by the opportunity to develop SHR-4849, which has monotherapy potential in SCLC and NETs. SHR-4849 is competitively well positioned with first-in-class potential in the DLL3 topo-I-payload ADC field, a therapeutic area that has demonstrated preliminary monotherapy clinical validation in SCLC," said Yujiro S. Hata, Chief Executive Officer and Founder, IDEAYA Biosciences. "In addition, SHR-4849 accelerates IDEAYA’s strategic objective to develop rational clinical combinations of topo-payload based ADCs with our PARG inhibitor IDE161, where we observe enhanced preclinical combination efficacy versus evaluated topo-payload ADCs alone," said Daniel A. Simon, Chief Business Officer, IDEAYA Biosciences.

Frank Jiang, Chief Strategy Officer and Board Director, Hengrui Pharma, said "SHR-4849 is a novel DLL3 targeting ADC showing encouraging early clinical signals in small-cell lung cancer with a manageable safety profile. We are delighted to partner with IDEAYA to support the development of this ADC globally, which furthers our goal of delivering innovative medicines for the benefit of patients around the world."

SHR-4849 has shown promising antitumor activity in preclinical studies, including tumor regression as a monotherapy in multiple models. This drug is currently being evaluated in a Phase 1 clinical trial for advanced solid tumors in China (NCT06443489). In the ongoing Phase 1 dose escalation, SHR-4849 has reached therapeutic dose levels where multiple partial responses have been observed as of the data cut-off date of December 10, 2024. Among 11 evaluable small cell lung cancer (SCLC) subjects treated at therapeutic dose levels, 8 partial responses by RECIST 1.1 were observed, resulting in an overall response rate of ~73% (including both confirmed and unconfirmed responses, all unconfirmed responses were pending further evaluation). As of the data cut-off date, treatment related adverse events (TRAEs) were predominantly Grade 1 or 2, and the Phase 1 dose escalation is ongoing with no reported drug-related discontinuations, and the maximum tolerated dose has not yet been reached. The most common TRAEs observed were white blood cell count decreased, anemia, neutrophil count decreased, nausea and platelet count decreased.

IDEAYA is targeting to file a US IND for SHR-4849 in the first half of 2025.

DLL3 has been reported to be expressed in multiple solid tumor types, including in SCLC and Neuroendocrine Tumors at approximately 85% and 20-40%, respectively, based on the Human Protein Atlas database. DLL3 has limited extracellular expression in normal tissues, making it a promising therapeutic target in these tumor types, for which there remains significant unmet medical need.

Under the terms of the agreement, Hengrui Pharma is eligible to receive upfront and milestone payments totaling $1.045 billion, including a $75m upfront fee, up to $200m in development and regulatory milestone payments, plus commercial success-based milestones. Hengrui is also eligible to receive mid-single to low-double digit royalties on net sales outside of Greater China. The upfront and projected research and development costs, including potential milestone payments, does not change the earlier provided IDEAYA guided cash out runway of at least 2028.

On December 29, 2024 CEL-SCI Corporation ("CEL-SCI" or the "Company") (NYSE American: CVM), a Phase 3 cancer immunotherapy company, reported the pricing of a best-efforts public offering of 16,130,000 shares of its common stock (or pre-funded warrants ("Pre-Funded Warrants") in lieu thereof). Each share of common stock (or Pre-Funded Warrant) is being sold at a public offering price of $0.31 per share (inclusive of the Pre-Funded Warrant exercise price) (Press release, Cel-Sci, DEC 29, 2024, View Source [SID1234649353]). Total gross proceeds from the offering, before deducting the placement agent’s fees and other offering expenses, are expected to be approximately $5,000,000. The offering is expected to close on December 31, 2024, subject to satisfaction of customary closing conditions.

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The Company intends to use the net proceeds from the offering to fund the continued development of Multikine, general corporate purposes, and working capital.

ThinkEquity is acting as sole placement agent for the offering.

The securities will be offered and sold pursuant to a shelf registration statement on Form S-3 (File No. 333-265995), including a base prospectus, filed with the U.S. Securities and Exchange Commission (the "SEC") on July 1, 2022, and declared effective on July 15, 2022. The offering will be made only by means of a written prospectus. A final prospectus supplement and accompanying prospectus describing the terms of the offering will be filed with the SEC on its website at www.sec.gov. Copies of the prospectus supplement and the accompanying prospectus relating to the offering may also be obtained, when available, from the offices of ThinkEquity, 17 State Street, 41st Floor, New York, New York 10004.

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