On January 29, 2024 Checkpoint Therapeutics, Inc. ("Checkpoint") (Nasdaq: CKPT), a clinical-stage immunotherapy and targeted oncology company, reported that it has entered into a definitive agreement with a single healthcare-dedicated institutional investor for the issuance and sale of an aggregate of 7,756,233 shares of its common stock (or common stock equivalents in lieu thereof) at a purchase price of $1.805 per share of common stock (or per common stock equivalent in lieu thereof), in a registered direct offering priced at-the-market (Press release, Checkpoint Therapeutics, JAN 29, 2024, View Source [SID1234639678]). In addition, in a concurrent private placement, Checkpoint will issue and sell unregistered warrants to purchase up to 7,756,233 shares of common stock. The warrants will have an exercise price of $1.68 per share, will be exercisable immediately upon issuance and will expire five years following the issuance date.

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

The closing of the offering is expected to occur on or about January 31, 2024, subject to the satisfaction of customary closing conditions. The gross proceeds from the offering are expected to be approximately $14 million. Checkpoint intends to use the net proceeds of this offering for working capital and general corporate purposes, including funding the planned resubmission of its Biologics License Application ("BLA") for cosibelimab.

The shares of common stock (or common stock equivalents) described above (but not the unregistered warrants issued in the concurrent private placement or the shares of common stock underlying such unregistered warrants) are being offered by Checkpoint pursuant to a shelf registration statement on Form S-3 (File No. 333-270843) that was previously filed with the Securities and Exchange Commission ("SEC") on March 24, 2023, and subsequently declared effective on May 5, 2023. The shares of common stock (or common stock equivalents) offered in the registered direct offering are being offered only by means of a prospectus, including a prospectus supplement, forming a part of the effective registration statement. A final prospectus supplement and 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 at www.sec.gov. Electronic copies of the final prospectus supplement and the accompanying base prospectus relating to the offering, when available, may also be obtained by contacting 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 unregistered warrants described above 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 underlying shares of common stock may not be offered or sold in the United States except pursuant to an effective registration statement with the SEC or an applicable exemption from the registration requirements of the Securities Act and such applicable state securities laws.

This press release does not constitute an offer to sell or a solicitation of an offer to buy the securities in this offering, 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 January 29, 2024 Alligator Bioscience (Nasdaq Stockholm: ATORX) reported positive top-line results from the OPTIMIZE-1 Phase 2 study of the company’s lead asset mitazalimab in 1st line metastatic pancreatic cancer (Press release, Alligator Bioscience, JAN 29, 2024, View Source [SID1234639677]). The open-label, multi-center study assessed the safety and efficacy of mitazalimab (CD40 mAb agonist) in combination with standard of care chemotherapy mFOLFIRINOX, in previously untreated, chemotherapy naive patients.

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The study achieved its primary endpoint with the top-line results demonstrating a confirmed Objective Response Rate (ORR) of 40.4%, an unconfirmed ORR of 50.9% and a disease control rate (DCR) of 79% in 57 evaluable patients, as per the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). This compares favorably to the ORR of 31.6% reported in a similar patient population treated with FOLFIRINOX alone.[1]

The cut-off time for analysis was November 14, 2023 with a median follow-up duration of 12.7 months. At the time of the analysis, a total of 29 (51%) patients were still alive, of these 18 (32%) were still on treatment. The longest ongoing treatment duration was 23 months. Three patients demonstrated complete remission of their target lesions. The study further demonstrated:

Median Overall Survival (mOS) of 14.3 months at the time of analysis and expected to improve as majority of the patients remain alive, comparing favorably to the 11.1 months demonstrated by FOLFIRINOX[1], and more recently by NALIRIFOX in the NAPOLI 3 Phase 3 trial[2]
An unprecedented median Duration of Response (DoR) of 12.5 months, compared to 5.9 months with FOLFIRINOX[1], and the 7.3 months demonstrated by NALIRIFOX[2]
The 12-month survival rate was 59.3% compared to 48.1% for FOLFIRINOX[1] and 45.6% for NALIRIFOX[2]
Median Progression Free Survival (PFS) of 7.7 months, compared to 6.4 months with FOLFIRINOX[1], and the 7.4 months demonstrated by NALIRIFOX[2]
Mitazalimab’s manageable safety and tolerability profile supporting long-term administration in combination with mFOLFIRINOX was confirmed
As the majority of patients remain alive at the time of analysis, Overall Survival and Durability of Response are expected to improve further with ongoing treatment and follow-up.

"We are very pleased to announce that the OPTIMIZE-1 study has successfully met its primary endpoint, with the data demonstrating that when combined with mFOLFIRINOX, mitazalimab provides significant survival benefit to pancreatic cancer patients compared to the standard of care," said Søren Bregenholt, CEO of Alligator Bioscience. "The unprecedented duration of response is to us a clear confirmation of the strong immune activation that mitazalimab triggers, which translates into a much improved overall survival. As of today, more than half of the patients are still in the study and we expect these promising data to improve even further."
"It is very rewarding for us to see the OPTIMIZE-1 top-line results demonstrate the clear clinical signal and survival benefit of mitazalimab in combination with mFOLFIRINOX," said Prof. Jean-Luc van Laethem, Head of the Digestive Oncology Clinic in the Gastroenterology Department of Erasmus Hospital (ULB) Brussels and Principal Investigator of the OPTIMIZE-1 trial. "Metastatic pancreatic cancer is particularly hard to treat due to its highly complex and aggressive nature, so for mitazalimab to have delivered such data in previously untreated patients is a remarkable and promising outcome."
"Successfully meeting its primary endpoint, together with a very long durability of response and median overall survival, is a highly encouraging result for the OPTIMIZE-1 study, which demonstrates mitazalimab’s potential in pancreatic cancer," said Dr. Zev Wainberg, Professor of Medicine at University of California, Los Angeles (UCLA) and co-director of the UCLA Gastrointestinal (GI) Oncology Program. "With current therapeutic options so limited, I remain highly optimistic that mitazalimab can have a significant impact on the way pancreatic cancer is treated and I look forward to the next stage of its clinical development. These data also warrant a broader evaluation of mitazalimab in other tumor types."
Phase 3 expected to start in early 2025
Alligator Bioscience has undertaken discussions with the US Food and Drug Administration (FDA) and has been able to establish a clear development and approval pathway for mitazalimab in pancreatic cancer. Based on the emerging data from the OPTIMIZE-1 study, FDA has provided additional guidance and has endorsed OPTIMIZE-1 as a Phase 3 enabling study. Consequently, mitazalimab can proceed directly to a global Phase 3 registration study, which Alligator is preparing to initiate in early 2025.

Mitazalimab has been granted orphan drug designation in pancreatic cancer by both FDA and the European Medicines Agency (EMA).

Webcast – Monday 29th January 2024 – 4 pm CET / 10am ET
A webcast will be held today, January 29th 2024, at 4pm CET / 10am ET, to discuss the top-line data of the mitazalimab OPTIMIZE-1 Phase 2 study with Dr. Zev Wainberg, Professor of Medicine at University of California, Los Angeles (UCLA) and co-director of the UCLA Gastrointestinal (GI) Oncology Program. A formal presentation will be followed by a Question and Answer Session.

Please use the following link to connect to the webcast via Alligator’s Youtube channel.

On January 29, 2024 (the "Effective Date"), Abbott Laboratories, an Illinois corporation ("Abbott"), reported to have entered into a Five Year Credit Agreement (the "Revolving Credit Agreement") with the lenders from time to time party thereto and JPMorgan Chase Bank, N.A., as administrative agent (Filing, 8-K, Abbott, JAN 29, 2024, View Source [SID1234639676]).

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The Revolving Credit Agreement provides Abbott with the ability to borrow up to $5 billion on an unsecured basis. Any borrowings under the Revolving Credit Agreement will mature and be payable on the fifth anniversary of the Effective Date. As of the date of this Current Report on Form 8-K, there are no outstanding borrowings under the Revolving Credit Agreement.

Abbott’s borrowings under the Revolving Credit Agreement will bear interest, at Abbott’s option, based on either a base rate or a SOFR rate, plus an applicable margin based on Abbott’s credit ratings in effect from time to time. Abbott will also pay to the lenders under the Revolving Credit Agreement certain customary fees.

The Revolving Credit Agreement contains representations and warranties and affirmative and negative covenants customary for unsecured financings of this type as well as customary events of default.

The foregoing description of the Revolving Credit Agreement is qualified in its entirety by reference to the full text of the Revolving Credit Agreement, a copy of which will be filed with Abbott’s annual report on Form 10-K for the period ending December 31, 2023.

Some of the lenders under the Revolving Credit Agreement and/or their respective affiliates have in the past performed, and may in the future from time to time perform, investment banking, financial advisory, lending and/or commercial banking services, or other services for Abbott and its subsidiaries, for which they have received, and may in the future receive, customary compensation and expense reimbursement.

On January 29, 2024 Vesicure Therapeutics reported its SiRNA technology offers distinct advantages over conventional approaches, with the potential to target virtually any gene (Press release, Vesicure Therapeutics, JAN 29, 2024, View Source [SID1234639674]). This technology has emerged as a great strategy for treating a range of diseases, including cancer, viral infections, and genetic disorders. In the US, five siRNA-based drugs have been approved, with several candidates undergoing clinical trials for conditions like COVID-19, HBV, cancer, and diabetes.

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Despite promising capabilities, siRNA drugs require efficient and safe delivery systems, as bloodstream clearance and limited tissue penetration beyond the liver remain as major challenges. Vesicure Therapeutics, a biotech company from Suzhou China, recently introduced their exosome-based siRNA delivery platform in a proof-of-concept study, by efficiently shuttling cell survival siRNA cargo to inhibit tumor growth through intratumoral (it) injection (BioRxiv: doi: View Source).

Taking a significant stride forward, in a new study, Vesicure extended the feasibility of this exosome-siRNA technology in targeting KRAS mutation in a CDX (Cell line-derived xenograft) mouse model (BioRxiv: doi: View Source). The data revealed that intravenously (iv) injected exosomes were enriched in tumors. These ‘KRAS siRNA carriers’ exhibited excellent tumor retention and growth inhibition without significant toxicity to mice. This advancement marks progress in developing exosomes for extrahepatic siRNA drug delivery for targeting previously deemed undruggable targets to address unmet therapeutic needs.

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On January 29, 2024 AstraZeneca and Daiichi Sankyo’s reported that supplemental Biologics License Application (sBLA) for Enhertu (trastuzumab deruxtecan) has been accepted and granted Priority Review in the US for the treatment of adult patients with unresectable or metastatic HER2-positive (immunohistochemistry [IHC] 3+) solid tumours who have received prior treatment or who have no satisfactory alternative treatment options (Press release, AstraZeneca, JAN 29, 2024, View Source [SID1234639638]).

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The sBLA is based on data from the ongoing DESTINY-PanTumor02 Phase II trial where Enhertu demonstrated clinically meaningful and durable responses leading to a clinically meaningful survival benefit in previously treated patients across HER2-expressing metastatic solid tumours, including biliary tract, bladder, cervical, endometrial, ovarian cancers, and other tumours. Data from other supporting trials in patients with HER2-positive IHC3+ tumours in the Enhertu clinical development programme, including DESTINY-Lung01 and DESTINY-CRC02, were also included in the submission.

Enhertu is a specifically engineered HER2-directed antibody drug conjugate (ADC) being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.

The Food and Drug Administration (FDA) grants Priority Review to applications for medicines that, if approved, would offer significant improvements over available options by demonstrating safety or efficacy improvements, preventing serious conditions or enhancing patient compliance.1 The Prescription Drug User Fee Act date, the FDA action date for their regulatory decision, is during the second quarter of 2024.

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "Today’s Priority Review for the first tumour-agnostic submission for Enhertu reflects the potential of this medicine to redefine the treatment of HER2-expressing cancers. Biomarkers for HER2 expression are already established in breast and gastric cancers, but we must now define them across tumour types. We will continue working closely with the FDA to bring this potential first tumour-agnostic HER2-targeted medicine and biomarker to patients as quickly as possible."

Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo, said: "The clinical benefit seen across HER2-expressing metastatic solid tumours in the DESTINY-PanTumor02 trial and ongoing data from the Enhertu clinical development programme continues to demonstrate the potential of this medicine beyond its approved indications. If approved, Enhertu could become the first HER2-directed therapy and antibody drug conjugate with a tumour-agnostic indication, providing patients with a potential new treatment option."

The sBLA is being reviewed under the Real-Time Oncology Review (RTOR) programme and Project Orbis, two initiatives of the FDA which are designed to bring safe and effective cancer treatments to patients as early as possible. RTOR allows the FDA to review components of an application before submission of the complete application. Project Orbis provides a framework for concurrent submission and review of oncology medicines among participating international partners.

Results from DESTINY-PanTumor02 were presented at the 2023 European Society for Medical Oncology Congress and simultaneously published in the Journal of Clinical Oncology.2

The safety profile observed across the trials was consistent with previous clinical trials of Enhertu with no new safety concerns identified.

The Priority Review follows receipt of Breakthrough Therapy Designation (BTD) in the US in August 2023 for Enhertu in metastatic HER2-positive solid tumours.

Notes

HER2 expression in solid tumours
HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of various tissue cells throughout the body and is involved in normal cell growth.3,4 In some cancers, HER2 expression is amplified or the cells have activating mutations.3,5 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and poor prognosis.6

While HER2-directed therapies have been used to treat breast, gastric, lung and colorectal cancers, more research is needed evaluating their potential role in treating other HER2-expressing solid tumour types.4,7,8

HER2 is an emerging biomarker in solid tumour types including biliary tract, bladder, cervical, endometrial, ovarian and pancreatic cancers.5 Testing is not routinely performed in these additional tumour types and as a result, available literature is limited. In these solid tumours, HER2-positive expression, classified as IHC 3+, has been observed at rates from 1% to 28%.9,10 There is an unmet need for effective therapies for certain HER2-expressing solid tumours, particularly for those who have progressed on or are refractory to standard of care therapies as there are currently no approved HER2-directed therapies for these cancers.4,11

DESTINY-PanTumor02
DESTINY-PanTumor02 is a global, multicentre, multi-cohort, open-label Phase II trial evaluating the efficacy and safety of Enhertu (5.4mg/kg) for the treatment of previously treated HER2-expressing tumours, including biliary tract cancer, bladder cancer, cervical cancer, endometrial cancer, ovarian cancer, pancreatic cancer or other tumours.

The primary efficacy endpoint of DESTINY-PanTumor02 is confirmed objective response rate (ORR) as assessed by investigator. Secondary endpoints include duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), safety, tolerability and pharmacokinetics.

DESTINY-PanTumor02 has enrolled 267 patients at multiple sites in Asia, Europe and North America. For more information about the trial, visit ClinicalTrials.gov.

DESTINY-Lung01
DESTINY-Lung01 is a global Phase II, open-label, two-cohort trial evaluating the efficacy and safety of Enhertu (5.4mg/kg or 6.4mg/kg) in patients with HER2-mutant (cohort 2, n=91) or HER2-overexpressing (defined as IHC 3+ or IHC 2+) [cohort 1 and 1a, n=90] unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC) who had progressed after one or more systemic therapies.

The primary endpoint is confirmed ORR by independent central review. Key secondary endpoints include DoR, DCR, PFS, OS and safety.

DESTINY-Lung01 enrolled 181 patients at multiple sites, including Asia, Europe and North America. For more information about the trial, visit ClinicalTrials.gov.

DESTINY-CRC02
DESTINY-CRC02 is a global, randomised, two arm, parallel, multicentre Phase II trial evaluating the efficacy and safety of two doses (5.4mg/kg or 6.4mg/kg) of Enhertu in patients with locally advanced, unresectable or metastatic HER2-positive colorectal cancer of BRAF wild-type, or RAS wild-type and RAS mutant tumour types previously treated with standard therapy.

The trial was conducted in two stages. In the first stage, patients (n=80) were randomised 1:1 to receive either 5.4mg/kg or 6.4mg/kg of Enhertu. In the second stage, additional patients (n=42) were enrolled in the 5.4mg/kg arm.

The primary endpoint is confirmed ORR as assessed by blinded independent central review. Secondary endpoints include DoR, DCR, investigator-assessed confirmed ORR, clinical benefit ratio, PFS, OS and safety.

DESTINY-CRC02 enrolled 122 patients at multiple sites in Asia, Europe and North America. For more information about the trial, visit ClinicalTrials.gov.

Enhertu
Enhertu is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. Enhertu consists of a HER2 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads, (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

Enhertu (5.4mg/kg) is approved in more than 55 countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received a (or one or more) prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial.

Enhertu (5.4mg/kg) is approved in more than 45 countries for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/in-situ hybridisation [ISH]-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.

Enhertu (5.4mg/kg) is approved in more than 30 countries worldwide for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer whose tumours have activating HER2 (ERBB2) mutations, as detected by a locally or regionally-approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 trial. Continued approval in the US for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Enhertu (6.4mg/kg) is approved in more than 30 countries for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial and/or DESTINY-Gastric02 trial.

Enhertu development programme
A comprehensive clinical development programme is underway globally, evaluating the efficacy and safety of Enhertu monotherapy across multiple HER2-targetable cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.