On February 5, 2024 Novartis reported that it has entered into an agreement to make a voluntary public takeover offer to acquire MorphoSys AG (FSE: MOR; NASDAQ: MOR), a Germany-based, global biopharmaceutical company developing innovative medicines in oncology (Press release, Novartis, FEB 5, 2024, View Source [SID1234639847]). The acquisition, which is subject to customary closing conditions, including a minimum acceptance threshold of 65% of outstanding shares tendered in the takeover offer and regulatory approvals, further expands and complements Novartis pipeline in oncology, one of its priority therapeutic areas, while also enhancing Novartis global footprint in hematology.

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Upon completion of the acquisition, Novartis will own pelabresib (CPI-0610), a novel and potentially practice changing treatment option with a well-tolerated safety profile provided in combination with ruxolitinib for patients with myelofibrosis (MF). It will also include tulmimetostat (CPI-0209), an early-stage investigational dual inhibitor of enhancer of zeste homolog 1 and 2 (EZH1 and EZH2) proteins currently being tested in patients with solid tumors or lymphomas.

Pelabresib in combination with ruxolitinib recently met its primary endpoint of spleen volume reduction in the Phase 3 MANIFEST-2 study in JAK inhibitor-naive MF patients1. The combination also demonstrated favorable trends in symptom improvement as evidenced by key secondary endpoints of absolute and 50% change in total symptom score (TSS) at week 24 compared to baseline. All four clinical hallmarks of disease in myelofibrosis – splenomegaly, disease-associated symptoms, anemia and bone marrow fibrosis – were improved with the pelabresib and ruxolitinib combination. In the earlier Phase 2 MANIFEST trial, the third arm of the study with a patient population comparable to MANIFEST-2, showed durable improvements in both spleen volume and total symptom score up to week 602. Regulatory filing with the U.S. FDA is planned for the second half of 2024.

"We are excited about the opportunity of bringing pelabresib, a potential next-generation treatment combined with ruxolitinib, to people living with myelofibrosis, a rare and debilitating form of blood cancer," said Shreeram Aradhye, M.D., President, Development and Chief Medical Officer of Novartis. "With the planned acquisition of MorphoSys, we aim to further strengthen our leading pipeline and portfolio in oncology, adding to our capabilities and expertise. Building on our long-standing development partnership with MorphoSys, we look forward to continuing our work together to realize the full impact and value of their investigational medicines for patients with unmet needs."

Pelabresib is an investigational small molecule designed to promote anti-tumor activity by selectively inhibiting the function of bromodomain and extra-terminal domain (BET) proteins to decrease the expression of abnormally expressed genes in cancer. Pelabresib is also being studied in patients with essential thrombocythemia (ET), which is currently in Phase 2 in second line of treatment. Besides pelabresib, MorphoSys’ pipeline includes a broad portfolio of partnered assets of which some are in partnership with Novartis, including ianalumab (VAY736) which is studied across multiple immunological diseases and in hematology.

Transaction Details
Under the agreed transaction, which has been unanimously approved by the Board of Directors of both companies, Novartis will make a voluntary public takeover offer for all no-par value bearer shares of MorphoSys AG for EUR 68 per share (or an aggregate of EUR 2.7bn).

The transaction is subject to customary closing conditions, including acceptance of the takeover offer by at least 65% of MorphoSys AG’s outstanding shares and receipt of regulatory approvals and is expected to close in the first half of 2024. Until the transaction closes, MorphoSys AG will continue to operate as a separate, independent company.

About Pelabresib (CPI-0610)
Pelabresib (CPI-0610) is an investigational small molecule designed to promote anti-tumor activity selectively by inhibiting the function of bromodomain and extra-terminal domain (BET) proteins to decrease the expression of abnormally expressed genes in cancer. Pelabresib is being investigated as a treatment for myelofibrosis and has not yet been approved by any regulatory authorities. The development of pelabresib was funded in part by The Leukemia and Lymphoma Society.

About Myelofibrosis
Myelofibrosis is a blood cancer – belonging to a group of diseases called myeloproliferative neoplasms – caused by genetic abnormalities in bone marrow stem cells and characterized by four hallmarks: enlarged spleen, anemia, impaired bone marrow microenvironment causing fibrosis, and debilitating disease-associated symptoms, including severe fatigue, night sweats, itching, increased bleeding and significant pain caused by their enlarged spleen. For many living with myelofibrosis, the combination of symptoms often severely impacts their quality of life. At diagnosis, several factors, such as age, genetics and bloodwork, help determine a patient’s long-term prognosis. About 90% of newly diagnosed patients have intermediate- to high-risk disease, which has a worse prognosis and a higher likelihood of disease-associated symptoms. While JAK inhibitors, the current standard of care, address some aspects of the disease, no agent provides broad disease control. There is an urgent need for novel, well-tolerated therapeutic options capable of changing the natural course of myelofibrosis to provide patients with deep and durable responses across its four hallmarks.

About Tulmimetostat (CPI-0209),
Tulmimetostat (CPI-0209) is an investigational compound designed to exert anti-tumor activity by inhibiting the function of enhancer of zeste homolog 1 and 2 (EZH2 and EZH1) proteins to reactivate silenced genes like tumor suppressor genes. Tulmimetostat is being tested as a once-daily oral treatment in a Phase 1/2 trial (NCT04104776) in patients with advanced solid tumors or lymphomas, including ARID1A-mutated ovarian clear cell carcinoma and endometrial carcinoma, diffuse large B-cell lymphoma, peripheral T-cell lymphoma, BAP1-mutated mesothelioma and castration-resistant prostate cancer.

On February 5, 2024 Triumvira Immunologics, a clinical-stage company developing novel, targeted autologous and allogeneic T cell therapeutics that co-opt the natural biology of T cells to treat patients with solid tumors, reported that the first patient has been dosed in its TACTIC-3 trial, a Phase I/II study, (NCT05862324) investigating the safety and efficacy of autologous TAC-T cell asset, TAC101-CLDN18.2, targeting Claudin 18.2+ solid tumors (Press release, Triumvira Immunologics, FEB 5, 2024, View Source [SID1234639846]). TAC101-CLDN18.2 is a novel cell therapy based on genetically engineered autologous T cells expressing a T-cell Antigen Coupler (TAC) that harnesses the inherent signaling pathways of the native T cell receptor complex and targets Claudin 18.2, an epithelial transmembrane protein overexpressed in gastric cancer and several other solid tumor types.

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"Claudin 18.2 is a promising target for cell therapy," said Andreas Bader, Ph.D., Chief Scientific Officer of Triumvira Immunologics. "Among normal tissues, it is restricted to the stomach and hidden between neighboring cells. In gastric cancer and a few other solid tumors, however, it is accessible and abundantly expressed on tumor cell surfaces and, therefore, it represents a significant tumor selective opportunity to address these types of cancers."

"We are delighted to initiate this study at such a pivotal moment for Triumvira as we advance an exciting clinical program aimed at addressing a substantial therapeutic gap for solid tumors," said Deyaa Adib, M.D., Chief Medical Officer of Triumvira Immunologics. "TAC101-CLDN18.2 represents a unique new therapy in our pipeline that has the potential to provide a new therapeutic solution for CLDN18.2 positive solid tumors including gastric, lung, ovarian and pancreatic cancers. There are currently no other approved treatment options against CLDN18.2, and novel therapeutics in development, such as TAC101-CLDN18.2, offer hope to a patient segment that constitutes ~40% of the gastric cancer population in the U.S. alone. Through our TAC technology, which harnesses the inherent signaling pathways of native TCRs, we aspire to bring forward innovative, chemotherapy-sparing therapeutic strategies for solid tumors."

TACTIC-3 is a first-in-human study investigating TAC101-CLDN18.2 to evaluate the safety, recommended Phase II dose (RP2D), pharmacokinetic profile, and efficacy in subjects with CLDN18.2+ solid tumors who have been treated with at least 2 lines of prior therapy in Phase I and between 2-4 lines of prior therapy in Phase II. In each phase, subjects with pancreatic ductal adenocarcinoma may have been treated with 1 line of prior antineoplastic therapy. In addition, subjects who are being treated with the current lines of therapy with no demonstrated benefit may also be eligible on the condition that no measurable disease was reported at baseline as a starting reference point.

On February 5, 2024 Papyrus Therapeutics Inc., a biotechnology platform company for the development of potent, multi-cancer, tumor suppressor precision therapies for solid cancers, reported the upcoming poster presentation entitled "Oncolytic Vaccinia Virus Carrying OPCML Tumor Suppressor is active in Epithelial Ovarian Cancer" has been accepted for presentation at the forthcoming AACR (Free AACR Whitepaper) meeting in San Diego in the Immunology category from 9.00am – 12.30pm PT on April 10th (View Source) (Press release, Papyrus Therapeutics, FEB 5, 2024, View Source;utm_medium=rss&utm_campaign=papyrus-therapeutics-to-present-at-aacr-april-5-10-san-diego [SID1234639845]).

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The data demonstrate that vaccinia virus directed OPCML protein expression enhances OVV selectivity against ovarian cancer cells through direct oncolysis, inhibition of specific RTKs, suppression of angiogenesis, and activation of antitumor immune responses synergistically when combined with an anti-PD-1 inhibitor.

According to Papyrus’ co-founder / chief scientific officer, and renowned translational medical oncologist Hani Gabra, PhD FRCP, "A short treatment with novel OVV-OPCML / anti-PD-1 inhibitor combination showed a 50% increase in median survival in the mice studied, an encouraging outcome demonstrating promise as a targeted strategy for ovarian cancer treatment. This is important given the relatively poor treatment results with check-point inhibitors to date in ovarian cancer."

On February 5, 2024 ImmunityBio, Inc. (NASDAQ: IBRX), a clinical-stage immunotherapy company, reported that findings from Patient-Reported Outcomes (PROs) of participants in the phase 2/3 QUILT 3.032 study of N-803 plus BCG in BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) were published by the peer-reviewed journal Urology Practice (Press release, ImmunityBio, FEB 5, 2024, View Source [SID1234639844]). These PROs support the positive interim results from the study published in NEJM Evidence, wherein 71% of patients in cohort A with CIS with or without Ta/T1 disease achieved a complete response.

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The published PROs based on a May 16, 2022 data cutoff indicate that both physical function and global health as self-reported by QUILT 3.032 participants with BCG-unresponsive NMIBC CIS (cohort A) or papillary disease (cohort B), remained stable over the 2-year course of the study for patients who completed the PRO questionnaires and reached 24 months on-study. In addition, overall both cohort A and B participants who reached month 24 on-study and also completed an NMIBC-specific questionnaire focusing on the challenges of bladder cancer, also reported no decline of their health or urinary tract-related symptoms while in the study. Overall, participants who achieved a complete response with the novel combination therapy reported better physical function by month six of the study than those who did not achieve a complete response.

"The self-reported stability of health and physical function over the course of the study by the participants reflect another aspect of safety and tolerability of this new combination therapy," said Patrick Soon-Shiong, M.D., Executive Chairman and Global Chief Scientific and Medical Officer at ImmunityBio. "Taken together with the positive response rate in cohort A of over 70%, the persistence of responses and cystectomy avoidance, these QoL findings suggest a favorable risk-benefit ratio for this potential new therapeutic option for patients with BCG-unresponsive bladder cancer."

The finding of relative stability of global health and physical function during the course of the study is similar to that reported by others for BCG monotherapy, suggesting the novel combination is as tolerable as treatment with BCG alone.

"Many current therapies for bladder cancer slow disease progression but can cause debilitating side effects," said Principal Investigator Karim Chamie, M.D., Associate Professor of Urology at UCLA. "The data from the QUILT 3.032 Quality of Life study suggest that many patients not only have a durable response but also report no decline in physical function, which is very important for these patients."

QUILT 3.032 Study Details

The ongoing phase 2/3 open-label multicenter registrational study QUILT 3.032 (NCT03022825) is evaluating the safety and efficacy of the investigational interleukin-15 superagonist N-803 (also known as Anktiva and nogapendekin alfa inbakicept, NAI) in combination with a standard therapy for NMIBC, bacillus Calmette-Guerin (BCG), in patients who failed or in whom cancer returned after BCG monotherapy, and thus were diagnosed as BCG-unresponsive. The study comprises three cohorts, with cohort A enrolling patients with carcinoma in situ (CIS) with or without Ta/T1 disease and cohort B enrolling patients with high grade Ta/T1 papillary disease. Both cohorts A and B received combination N-803 plus BCG therapy. Cohort C patients, with CIS +/- Ta/T1 disease received N-803 monotherapy.

The primary end point is the incidence of CR at the 3- or 6-month assessment visit for cohorts A and C, and the disease-free survival (DFS) rate at 12 months for cohort B.
Durability, cystectomy avoidance, progression-free survival, disease-specific survival (DSS), and overall survival are secondary end points for cohort A.
Cohort C was discontinued due to a low response rate with N-803 monotherapy, per study design.
The FDA has accepted for review ImmunityBio’s resubmission of its biologics license application (BLA) for N-803 plus BCG for the treatment of BCG-unresponsive NMIBC CIS with or without Ta or T1 disease, and has set a user fee goal date (PDUFA date) of April 23, 2024.
Bladder cancer is the 10th most-commonly diagnosed cancer, with approximately 80% of newly diagnosed cases being NMIBC. Intravesical (directly to the bladder) instillation of BCG after removal of cancer tissue from the lining of the bladder (transurethral resection of the bladder tumor; TURBT) is Standard-of-Care (SoC) for intermediate and high-risk NMIBC patients, but up to 40% of patients will fail BCG therapy and ~50% will relapse after an initial response and given a diagnosis of being BCG-unresponsive. Therapies approved by the FDA for this indication include pembrolizumab, nadofaragene, combined gemcitabine and docetaxel, and valrubicin. Radical cystectomy – surgical removal of the bladder – is also an option for these patients. QUILT 3.032 is being conducted to address the need for a safe, effective therapeutic option for BCG-unresponsive NMIBC patients that provides an opportunity for avoidance of radical cystectomy.

N-803 is investigational. Safety and efficacy have not been established by any Health Authority or Agency, including the FDA.

On February 5, 2024 Immix Biopharma, Inc. (Nasdaq: IMMX) (the "Company"), a clinical-stage biopharmaceutical company trailblazing cell therapies in autoimmune disease, reported that it intends to offer and sell shares of its common stock in an underwritten public offering (Press release, Immix Biopharma, FEB 5, 2024, View Source [SID1234639843]). All of the shares of common stock in the underwritten public offering are to be sold by the Company. The Company also expects to grant the underwriters a 30-day option to purchase additional shares of common stock offered in the public offering. The offering is subject to market conditions, and there can be no assurance as to whether or when the offering may be completed, or as to the actual size or terms of the offering.

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The Company intends to use the net proceeds from the proposed offering for NXC-201 clinical trials, working capital and general corporate purposes.

Titan Partners Group, LLC, a division of American Capital Partners, LLC, is acting as sole book-running manager for the offering.

A shelf registration statement relating to the shares of common stock to be issued in the proposed offering was filed with the Securities and Exchange Commission ("SEC") and declared effective by the SEC. A preliminary prospectus supplement relating to the proposed offering has been filed with the SEC and is available on the SEC’s website at View Source A final prospectus supplement describing the terms of the proposed offering will be filed with the SEC. The offering will be made only by means of the preliminary prospectus supplement and the accompanying base prospectus, as may be further supplemented by any free writing prospectus and/or pricing supplement that the Company may file with the SEC. Copies of the preliminary prospectus supplement and accompanying base prospectus relating to the offering may be obtained from Titan Partners Group, LLC, a division of American Capital Partners, LLC, 4 World Trade Center, 29th Floor, New York, NY 10007, by email at [email protected], or by calling (929) 833-1246.

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