On June 26, 2024 Korean scientists reported to have investigated HVH-2930, an innovative HSP90 inhibitor in reshaping HER2-positive breast cancer treatment (Press release, Korea University, JUN 26, 2024, View Source [SID1234644559]). Unlike previous HSP90 inhibitors, this compound circumvents limitations by bypassing heat shock response induction. It demonstrates promising efficacy in inducing cancer cell apoptosis and effectively overcomes treatment resistance. In preclinical studies, HVH-2930 showed substantial promise, offering hope for better treatment outcomes. Its potential for diverse HER2-overexpressing malignancies indicates a paradigm shift in cancer therapy, anticipating enhanced effectiveness and increased availability.

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HER2-positive breast cancer, known for its aggressive nature due to the overexpression of the HER2 protein, poses significant challenges in treatment. Current standard treatments for HER2-positive breast cancer typically involve a combination of HER2-targeted therapies like trastuzumab, chemotherapy, and hormone therapy. However, the emergence of resistance highlights the need for novel approaches for improved outcomes.

In this relentless pursuit of treatment solutions, a team of researchers at Korea University led by Professor Jae Hong Seo have achieved a significant milestone with the development of HVH-2930, a promising inhibitor targeting heat shock protein 90 (HSP90), the findings of which were published in Theranostics on 31 March 2024. Prof. Seo shares, "We have highlighted the pivotal role of HSP90, an oncogenic protein, in fueling tumor growth by activating key receptor tyrosine kinases, including HER2. While previous N-terminal HSP90 inhibitors faced challenges like inducing the heat shock response (HSR) and toxicity, HVH-2930, a C-terminal HSP90 inhibitor, shows promise."

The study utilized both in vivo and in vitro methods to investigate HER2-positive breast cancer and potential treatments. In laboratory settings, breast cancer cells were cultured alongside normal mammary cells, using advanced cytometry techniques to assess cell viability, apoptosis, and functionality. Additionally, protein interactions were studied to uncover underlying molecular processes. In mouse models, tumor cell implantation was used to study tumor growth dynamics and treatment responses.

The findings revealed that HVH-2930 effectively induced apoptosis in breast cancer cells without triggering the heat shock response (HSR), a notable feature that distinguishes it from other treatments. By selectively targeting HSP90, HVH-2930 downregulated HER2 signaling, crucial in breast cancer progression. Impressively, in xenograft mouse models, HVH-2930 inhibited tumor growth, angiogenesis, and cancer stem cell-like properties without causing toxicity. Moreover, when combined with paclitaxel, HVH-2930 exhibited a synergistic antitumor effect, suggesting its potential as a promising therapeutic strategy for HER2-positive breast cancer. These results signify a significant advancement in targeting the HSP90 chaperone machinery for breast cancer treatment.

Prof. Seo shares "HVH-2930 stands as a groundbreaking advancement in meeting the critical needs of HER2-positive breast cancer patients, notably those resistant to trastuzumab. With its potential application in other HER2-overexpressing cancers like gastric and esophageal cancers, it holds promise for treating a wider range of patients. Moreover, its anticipated affordability compared to current therapies could significantly enhance accessibility, particularly in resource-limited settings such as underdeveloped countries."

On June 26, 2024 Repare Therapeutics Inc. ("Repare" or the "Company") (Nasdaq: RPTX), a leading clinical-stage precision oncology company, reported positive initial data from the ongoing Phase 1 MINOTAUR clinical trial evaluating lunresertib (RP-6306) in combination with FOLFIRI in patients with advanced solid tumors (Press release, Repare Therapeutics, JUN 26, 2024, View Source [SID1234644560]). The data are being presented in a mini oral presentation by Elisa Fontana, M.D., Ph.D., Medical Director, Sarah Cannon Research Institute UK at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Gastrointestinal (GI) Cancers Congress 2024, being held June 26-29 in Munich, Germany.

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"The initial results from the ongoing MINOTAUR trial demonstrate promising efficacy and tolerability data of lunresertib plus FOLFIRI in genomically defined tumors that represent 20% of all gastrointestinal cancers," said Dr. Elisa Fontana. "These early data suggest that lunresertib plus FOLFIRI combination therapy may effectively treat patients with CCNE1 amplification and deleterious FBXW7 mutations, who often suffer from poor prognosis and lack approved treatment options. We are excited by the prolonged benefit that some patients continue to experience on therapy, especially in colorectal cancer, and the favorable tolerability of this lunresertib combination therapy across tumor types, unlike other agents combined with irinotecan."

Lunresertib is a first-in-class precision oncology small molecule PKMYT1 inhibitor that targets CCNE1 amplification, FBXW7 and PPP2R1A alterations in solid tumors. Lunresertib is being evaluated in combination with other therapies across several Phase 1 and Phase 2 clinical trials, as well as in multiple investigator-sponsored trials.

Key Initial Findings from the Phase 1 MINOTAUR Clinical Trial:

MINOTAUR (NCT05147350) is a Phase 1, multi-center, open-label, dose-scalation study to evaluate safety, pharmacokinetics, pharmacodynamics and preliminary anti-tumor activity of lunresertib in combination with FOLFIRI in advanced solid tumors. Primary objectives of the study were safety and tolerability, and determination of the recommended Phase 2 dose (RP2D) and schedule. Secondary objectives were pharmacokinetics, preliminary evidence of anti-tumor activity, pharmacodynamics, and circulating tumor DNA (ctDNA) monitoring. As of May 2, 2024, the cutoff date for the data presented at the ESMO (Free ESMO Whitepaper) GI Congress, 38 patients were enrolled in the clinical trial.

Preliminary RP2D established as 60mg BID lunresertib continuous plus standard FOLFIRI
Promising efficacy in heavily pretreated population with tumors that harbor CCNE1 amplification and FBXW7 mutation alterations
Overall response (OR) across tumor types was 18.2% (n=33), including four confirmed and two unconfirmed partial responses (PR), regardless of prior irinotecan exposure
Prolonged clinical benefit rate (CBR) across tumor types, primarily digestive system tumors, was 51.5%, including 46.7% of patients with recurrent colorectal cancer (CRC)
Patients with CRC (n=15) had prolonged duration of therapy, with 40% (2/5) of irinotecan-naïve patients and 20% (2/10) of irinotecan-experienced patients on treatment for over nine months, compared to clinical benchmarks of 20% and 5-10%, respectively
ctDNA molecular response rate was 61% among evaluable patients (14/23)
Lunresertib combination therapy was well tolerated without excess toxicity above expected rates for lunresertib or standard FOLFIRI alone
No safety-related treatment discontinuations at preliminary RP2D
Neutropenia and leukopenia were the most common Grade 3/4 treatment-related adverse events (TRAE), consistent with that reported for FOLFIRI alone and reversible with FOLFIRI interruption
Rate of low-grade, reversible rash was consistent with lunresertib monotherapy experience
"The encouraging tolerability and early antitumor efficacy data and the potential duration of treatment advantage of the combination of lunresertib plus FOLFIRI in this heavily pretreated patient population warrant further development in a randomized Phase 2 study," said Maria Koehler, MD, PhD, Executive Vice President and Chief Medical Officer of Repare. "Lunresertib in combination with FOLFIRI has the potential to provide a new therapeutic option targeting tumors harboring CCNE1 amplification and FBXW7 mutation alterations in gastrointestinal tumors, which are known to be associated with poor prognosis and where there are currently no approved treatment options."

On June 26, 2024, Coherus BioSciences, Inc., a Delaware corporation (the "Company"), reported to have entered into an Asset Purchase Agreement (the "Purchase Agreement") by and between the Company and Hong Kong King-Friend Industrial Company Ltd., a Hong Kong corporation ("HKF"). HKF is the parent company of Meitheal Pharmaceuticals, Inc., a Delaware corporation (Press release, Coherus Biosciences, JUN 26, 2024, View Source [SID1234644564]).

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Pursuant to the terms and subject to the conditions set forth in the Purchase Agreement, the Company agreed to divest its YUSIMRY (adalimumab-aqvh) franchise (the "Business") through the sale of certain assets, including YUSIMRY, intellectual property exclusively related to YUSIMRY, certain contracts related to YUSIMRY, YUSIMRY inventory, and all activities related to research and development of YUSIMRY, to HKF and the assumption of certain liabilities by HKF, including $17.0 million of inventory purchase commitments, but not including certain identified excluded assets and excluded liabilities (collectively, the "YUSIMRY Disposition") for upfront, all-cash consideration of $40.0 million paid on June 26, 2024.

The Purchase Agreement also provides for indemnification rights related to breaches of each party’s representations, warranties, covenants and certain other matters such as losses incurred by HKF for excluded assets or excluded liabilities or losses incurred by the Company for assumed liabilities. The indemnification obligations of each party are subject to the limitations set forth in the Purchase Agreement.

The Purchase Agreement contains customary representations, warranties and covenants related to the Company, the Business and the YUSIMRY Disposition that are subject, in some cases, to specified exceptions and qualifications contained in the Purchase Agreement. The covenants include, among other things, (a) an agreement for the Company to provide access to records related to the Business after the closing of the YUSIMRY Disposition and (b) an agreement to certain non-competition and non-solicitation agreements.

Pursuant to the Purchase Agreement, the closing of the YUSIMRY Disposition occurred on June 26, 2024.

The representations and warranties of the Company and HKF contained in the Purchase Agreement have been made solely for the benefit of the parties to the Purchase Agreement. In addition, such representations and warranties (a) have been made only for purposes of the Purchase Agreement, (b) have been qualified by confidential disclosures made to the Company and HKF in connection with the Purchase Agreement, (c) are subject to materiality qualifications contained in the Purchase Agreement which may differ from what may be viewed as material by investors, (d) were made only as of the date of the Purchase Agreement, or such other dates that are specified in the Purchase Agreement and (e) have been included in the Purchase Agreement for the purpose of allocating risk between the Company and HKF rather than establishing matters as facts. Accordingly, the Purchase Agreement is included with this filing only to provide investors with information regarding the terms of the Purchase Agreement, and not to provide investors with any other factual information regarding the Company or HKF or their respective subsidiaries, affiliates or businesses. Investors and security holders are not third-party beneficiaries under the Purchase Agreement and should not rely on the representations and warranties or any descriptions thereof as characterizations of the actual state of facts or condition of the Company or HKF or any of their respective subsidiaries, affiliates or businesses. Moreover, information concerning the subject matter of the representations and warranties may change after the date of the Purchase Agreement, which subsequent information may or may not be fully reflected in the Company’s public disclosures.

The foregoing description of the Purchase Agreement and the YUSIMRY Disposition is not complete and is qualified in its entirety by reference to the Purchase Agreement, which is filed as Exhibit 2.1 hereto and is incorporated herein by reference.

On June 26, 2024 Alligator Bioscience (Nasdaq Stockholm: ATORX) reported positive 18-month follow-up data from the OPTIMIZE-1 Phase 2 study of the company’s lead asset mitazalimab in 1st line metastatic pancreatic cancer (Press release, Alligator Bioscience, JUN 26, 2024, View Source [SID1234644545]). 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 naïve pancreatic cancer patients.
The data demonstrated a near doubling of the 18-month survival rate to 36.2% in patients treated with mitazalimab in combination with mFOLFIRINOX, compared to 18.6% reported with FOLFIRINOX[1] alone.

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The updated Median Overall Survival (mOS) was 14.9 months, up from 14.3 months at the time of first analysis, comparing favorably to the 11.1 months demonstrated by FOLFIRINOX[1] and more recently by NALIRIFOX[2].

Median follow-up duration for the updated analysis was 18.2 months, indicating the maturity of these outcomes. At the time of the analysis, a total of 17 (30%) patients were still alive, and of these 9 (16% overall) were still on treatment. The longest ongoing treatment duration was 24 months.

The follow-up data further demonstrate:

An additional late responding patient increased the confirmed Objective Response Rate (ORR; as per the Response Evaluation Criteria in Solid Tumors RECIST 1.1) to 42.1% from the 40.4% reported in the top-line readout, comparing favorably to the ORR of 31.6% reported in a similar patient population treated with FOLFIRINOX alone[1] and an ORR of 42% reported by NALIRIFOX[2]
An increase in the unconfirmed ORR to 54.4% was reported in 57 evaluable patients
The median Duration of Response (DoR) was 12.6 months, an unprecedented outcome in this aggressive disease and much longer compared to 5.9 months with FOLFIRINOX[1] and 7.3 months with NALIRIFOX[2]
Median Progression Free Survival (PFS) was 7.7 months, and a nearly 3-fold increase in the 12-month PFS rate was reported; 35.1% in OPTIMIZE-1 against 12.1% previously reported for FOLFIRINOX[1].
"These latest results from the OPTIMIZE-1 study of our lead asset provide a strong validation of the clear and sustained clinical benefit produced by mitazalimab when combined with mFOLFIRINOX in the treatment of first-line pancreatic cancer. In fact, mitazalimab increases your chance of being alive at the 18-month mark by 95 percent, compared to published FOLFIRINOX data," said Søren Bregenholt, CEO of Alligator Bioscience. "These highly promising outcomes warrant continued clinical development of mitazalimab in a confirmatory setting and we are committed to bringing mitazalimab to pancreatic cancer patients as fast as possible."
"These results clearly represent a remarkable outcome in pancreatic cancer, with the robust Duration of Response indicating highly consistent clinical benefit resulting in prolonged Overall Survival," 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. "Particularly noteworthy is the high proportion of patients surviving at the 18-month landmark, which most patients in this disease unfortunately do not see. With such a strong immunotherapeutic contribution, mitazalimab combined with mFOLFIRINOX has the potential to become the new treatment standard in pancreatic cancer, and we are eagerly awaiting the initiation of a randomized confirmatory study."
Top-line results from the OPTIMIZE-1 study were published in the world-leading oncology journal The Lancet Oncology and will also be presented at the upcoming ESMO (Free ESMO Whitepaper) Gastrointestinal Cancers Congress 2024 being held in Munich, Germany from June 26-29.

Phase 3 on track to start in first half of 2025
Alligator is continuing its preparations for the global Phase 3 registration study to evaluate mitazalimab in pancreatic cancer and the company remains on track to initiate the study in 2025. This follows Alligator’s discussions with the US Food and Drug Administration (FDA) which established a clear development and approval pathway for mitazalimab in pancreatic cancer.

In 2023, mitazalimab was granted orphan drug designation in pancreatic cancer by both the FDA and the European Medicines Agency (EMA).

On June 26, 2024 CNS Pharmaceuticals, Inc. (NASDAQ: CNSP) ("CNS" or the "Company"), a biopharmaceutical company specializing in the development of novel treatments for primary and metastatic cancers in the brain and central nervous system, reported it has entered into securities purchase agreements with health-care focused institutional investors for the purchase and sale of 568,000 shares of common stock in a registered direct offering and warrants to purchase up to 568,000 shares of common stock in a concurrent private placement (together with the registered direct offering, the "Offering") at a combined purchase price of $2.45 per share (Press release, CNS Pharmaceuticals, JUN 26, 2024, View Source [SID1234644546]). The warrants issued pursuant to the concurrent private placement will have an exercise price of $2.32 per share, will be exercisable immediately following the date of issuance and will expire 5 years from the initial exercise date.

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The closing of the Offering is expected to occur on or about June 27, 2024, subject to the satisfaction of customary closing conditions. The gross proceeds from the Offering are expected to be approximately $1.39 million before deducting financial advisory fees and other offering expenses payable by the Company. The Company intends to use the net proceeds from the Offering for working capital and general corporate purposes.

The common stock will be issued in a registered direct offering pursuant to an effective shelf registration statement on Form S-3 (File No. 333-279285) previously filed with the U.S. Securities and Exchange Commission (the "SEC"), under the Securities Act of 1933, as amended (the "Securities Act"), and declared effective by the SEC on May 17, 2024. The warrants will be issued in a concurrent private placement. A prospectus supplement describing the terms of the proposed registered direct offering will be filed with the SEC and once filed, will be available on the SEC’s website located at View Source

The private placement of the ordinary warrants and the underlying shares will be made in reliance on an exemption from registration under Section 4(a)(2) of the Securities Act and/or Regulation D thereunder. Accordingly, the securities issued in the concurrent private placement 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 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.