On November 13, 2024 BioNTech SE (Nasdaq: BNTX, "BioNTech") and Biotheus ("Biotheus") reported the signing of a definitive agreement for the acquisition of Biotheus, a clinical-stage biotechnology company dedicated to the discovery and development of novel antibodies to address unmet medical needs of patients with oncological or inflammatory diseases (Press release, BioNTech, NOV 13, 2024, View Source [SID1234648262]).

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With the acquisition, BioNTech will obtain full global rights to the late-stage clinical asset BNT327/PM8002, an investigational bispecific antibody targeting PD-L1 and VEGF-A. The transaction is part of BioNTech’s oncology strategy, aimed at enhancing the company’s capabilities to research, develop and commercialize combination therapies using BNT327/PM8002. Clinical trials with BNT327/PM8002 and the PD-(L)1 x VEGF bispecific class of drugs have demonstrated encouraging clinical activity in various tumor types including in patients with PD-L1-low and -negative tumors who have typically been less responsive to current checkpoint inhibitor treatments.

"The acquisition of Biotheus builds on our successful ongoing collaboration on BNT327/PM8002 and other investigational bispecific antibodies," said Prof. Ugur Sahin, M.D., Ph.D., CEO and co-founder of BioNTech. "We believe that BNT327/PM8002 has the potential to set a new standard of care in multiple oncology indications, surpassing traditional checkpoint inhibitors. We are committed to advancing its research and development in combination with our investigational mRNA vaccines, targeted therapies, and immunomodulators with the aim of enhancing outcomes for patients with solid tumors."

"We are thrilled to deepen our bond with BioNTech. We share the goal of advancing the development of BNT327/PM8002 for future combination therapies in the fight against cancer," said Xiaolin Liu, President, CEO, and Co-Founder of Biotheus. "We believe that BNT327/PM8002 holds significant potential across various tumor indications, and we have an exciting pipeline of innovative investigational assets under development including an antibody discovery and development platform. As we move forward, we are committed to leveraging our strengths with the aim of advancing transformative cancer treatments and enhance our ability to develop treatments for patients in need."

BNT327/PM8002 has shown encouraging efficacy and tolerability in patients across various tumor types, with more than 700 patients treated in clinical trials to date. Multiple registrational trials are planned to start in 2024 and 2025, evaluating BNT327/PM8002 plus chemotherapy in various solid tumor indications including in patients with small cell lung cancer, non-small cell lung cancer and triple-negative breast cancer. Additional trials will explore combining BNT327/PM8002 and BioNTech’s proprietary antibody-drug conjugates ("ADCs"). In June 2024, the evaluation of BNT327/PM8002 in combination with BNT325/DB-1305, a Trophoblast Cell-Surface Antigen 2 ("TROP2")-targeted ADC candidate developed by BioNTech in collaboration with Duality Biologics (Suzhou) Co., Ltd. ("DualityBio"), was initiated as part of an ongoing Phase 1/2 clinical trial (NCT05438329).

Under the terms of the agreement, BioNTech will pay Biotheus shareholders an upfront consideration of $800 million, predominantly in cash, with a small portion in American depositary shares ("ADS"), to acquire 100 percent of the issued share capital, subject to customary purchase price adjustments, plus additional performance-based contingent payments of up to $150 million if certain milestones are met. The transaction is expected to close in the first quarter of 2025, subject to the satisfaction of customary closing conditions, including regulatory approvals. The acquisition follows an initial exclusive global license and collaboration agreement between BioNTech and Biotheus, which closed in November 2023, granting BioNTech the rights to develop, manufacture and commercialize BNT327/PM8002 globally ex-Greater China.

Upon closing, BioNTech will gain full rights to Biotheus’ pipeline candidates and its in-house bispecific antibody drug conjugate capability. The acquisition will expand BioNTech’s footprint in China, adding a local research and development hub to conduct clinical trials. In addition, BioNTech will gain a state-of-the-art biologics manufacturing facility to contribute to its future global manufacturing and supply, and more than 300 Biotheus employees in R&D, manufacturing and enabling functions are expected to join the BioNTech workforce.

BioNTech’s Innovation Series R&D Day
BioNTech leadership will present additional details on the Biotheus transaction, as well as updates on the corporate strategy, commercial strategy and clinical progress across its pipeline during an edition of the company’s Innovation Series R&D Day on 14 November. The live webcast of the event will be available via this link and will begin at 4:30 pm CET (3:30 pm GMT, 10:30 am EST). A replay of the webcast will be available shortly after the event’s conclusion and archived on BioNTech’s website for one year.

About BNT327/PM8002
BNT327/PM8002 is an investigational bispecific antibody combining PD-L1 checkpoint inhibition with VEGF-A neutralization. The checkpoint inhibition is aimed at restoring T cells’ ability to recognize and destroy tumor cells while targeting VEGF-A is aimed at inhibiting tumor angiogenesis, which cuts off the blood and oxygen supply that feeds tumor cells and thus prevents the tumor from growing and proliferating. The combined blockade of the PD-(L)1 pathway and the VEGF-A driven angiogenesis has been shown to deliver synergistically enhanced anti-tumor immune responses in several solid tumor types.1,2 If successfully developed and approved, BioNTech aims to use this bispecific antibody candidate as a new therapeutic backbone in combination with other treatment modalities targeting different oncogenic pathways.

On November 13, 2024 Mural Oncology plc (Nasdaq: MURA), a clinical-stage immuno-oncology company developing novel, investigational engineered cytokine therapies designed to address areas of unmet need for patients with a variety of cancers, reported financial results for the third quarter of 2024 and provided an update on pipeline progress (Press release, Mural Oncology, NOV 13, 2024, View Source [SID1234648283]).

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"Mural launched as a stand-alone company one year ago with a mission to shepherd in the second wave of immuno-oncology for patients—IO 2.0—and we believe we are well on the path to realize that vision. With our deep expertise of protein engineering and cancer biology, we are working to address key limitations with cytokine therapies and unleash their full potential. We are now focused on clinical execution, with major readouts of our two potentially registrational studies of nemvaleukin in the first half of next year, and commercial readiness. We are also deepening our pipeline with candidate nominations for our IL-18 and IL-12 programs expected by the end of this year," said Caroline Loew, Ph.D., CEO of Mural Oncology.

Clinical Progress & Upcoming Catalysts:

Mural’s late-stage trials of nemvaleukin alfa (nemvaleukin), an engineered fusion protein designed to leverage Interleukin-2’s (IL-2) antitumor effects while mitigating its hallmark toxicities, remain on track. The company shared new information related to study design, statistical assumptions, and study execution at a virtual Investor Day in September 2024, including:

Completion of enrollment in ARTISTRY-7, the company’s potentially registrational phase 3 trial in platinum-resistant ovarian cancer (PROC), with a total of 456 patients enrolled. The study is comparing the combination of nemvaleukin and pembrolizumab versus investigator’s choice single agent chemotherapy. Mural expects to report interim overall survival (OS) results in late Q1 or early Q2 based on an analysis performed at approximately 75% of OS events. If the hazard ratio meets the bar for success (0.727, or a 27.3% reduction in the risk of death assuming exactly 215 OS events), the company plans to file a Biologics License Application (BLA) in 2025 subject to discussions with the U.S. Food and Drug Administration (FDA). The company expects to report final results in the second quarter of 2026.
Completion of enrollment in ARTISTRY-6, Cohort 2, the company’s potentially registrational phase 2 study of single agent nemvaleukin in patients with unresectable or metastatic mucosal melanoma, with 92 patients enrolled. Mural anticipates reporting top-line results from cohort 2 of ARTISTRY-6 in Q2 of 2025. The target response rate is 25%. Mural believes that in this rare and highly aggressive tumor with poor outcomes even in the first line setting, demonstrating durable responses with a response rate of 20-25% would be meaningful for patients, and would support a discussion with the FDA regarding a BLA submission and potential accelerated approval.
For the full updates from Mural’s Investor Day, please visit the webcast on our Events & Presentations page.

Mural is also evaluating a less-frequent intravenous (LFIV) dose of nemvaleukin in patients with cutaneous melanoma in ARTISTRY-6, Cohort 3 (monotherapy) and Cohort 4 (combination with pembrolizumab). The company continues to expect preliminary data readouts in the monotherapy cohort in the first half of 2025, and in the combination cohort in the second half of 2025.

Preclinical Program Updates:

Mural plans to nominate development candidates for its IL-18 and IL-12 programs by the end of 2024. The company expects to submit an Investigational New Drug (IND) Application for its IL-18 program to the FDA in Q4 2025.

Other Recent Corporate Highlights:

In September, Mural announced the appointment of Sachiyo Minegishi to its board of directors and chair of the Audit Committee. Ms. Minegishi brings over two decades of biopharma experience, with a focus on corporate strategy, finance, development, and commercialization. She is currently the Chief Operating Officer at Rectify Pharmaceuticals, driving corporate and financing strategy to advance its lead program from discovery to clinical stage. Prior to Rectify, she was Chief Financial Officer at Akouos, Inc., where she led corporate finance and business development strategy and played a key role in the acquisition of the company by Eli Lilly.

In October, Mural continued to prepare for potential launch readiness by creating a new commercial division in the company. Brandon Kotaniemi, SVP of Commercial, will drive Mural’s commercial strategy as the company prepares for the potential BLA submission and launch of nemvaleukin. He will also partner closely with Mural’s development team as the company looks to move its IL-18 program into the clinic.

In November, Mural presented clinical and preclinical data at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper). The three poster presentations included tumor microenvironment pharmacodynamic data from the phase 1/2 ARTISTRY-3 study of nemvaleukin as well as data from Mural’s two preclinical research programs in IL-18 and IL-12.

Financial Results for the Quarter Ended September 30, 2024:

Cash Position: As of September 30, 2024, cash, cash equivalents, and marketable securities were $175.5 million.

R&D Expenses: Research and development expenses were $27.6 million for the third quarter of 2024 compared to $40.4 million for the third quarter of 2023. This decrease in R&D expenses was primarily due to different team composition compared to the personnel previously allocated to us by Alkermes plc (Alkermes), our former parent prior to the separation, as well as decreased spend on the ARTISTRY-1 and ARTISTRY-2 trials as activities related to these trials wound down in 2023, and decreased spend on the ARTISTRY-7 trial due to the timing of patient enrollment.

G&A Expenses: General and administrative expenses were $6.5 million for the third quarter of 2024 compared to $6.0 million for the third quarter of 2023. This increase in G&A expenses was primarily due to costs associated with operating as a standalone company after the separation. This includes professional fees as well as differences in costs of insurance and taxes compared to amounts previously allocated to us by Alkermes prior to the separation.

Net Loss: Net loss was $31.8 million for the third quarter of 2024 compared to $51.3 million for the third quarter of 2023.

Financial Guidance:
The company reaffirms guidance that its cash, cash equivalents, and marketable securities as of September 30, 2024 are expected to fund its operations into the fourth quarter of 2025.

As noted previously, management forecasts lower operating expenses in 2025 versus 2024 due to the timing of clinical trial expenses.

On November 13, 2024 Tyra Biosciences, Inc. (Nasdaq: TYRA), a clinical-stage biotechnology company focused on developing next-generation precision medicines that target large opportunities in Fibroblast Growth Factor Receptor (FGFR) biology, reported that company management will participate in the following investor conferences (Press release, Tyra Biosciences, NOV 13, 2024, View Source [SID1234648307]):

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Jefferies London Healthcare Conference, November 19-21st, 2024:

Todd Harris, CEO of TYRA, will participate in a fireside chat on Tuesday, November 19th, at 2:00 pm GMT.
TYRA management will also participate in one-on-one investor meetings and B2B meetings.
36th Annual Piper Healthcare Conference, December 3-5th, 2024, New York:

Mr. Harris will participate in a fireside chat on Wednesday, December 4th, at 10:30 am ET.
TYRA management will also participate in one-on-one meetings with investors.
A live and archived webcast of the fireside chats will be available via the For Investors page on the TYRA website.

On November 13, 2024 CEL-SCI Corporation reported that it recently reached an agreement with Dr. Nabil F. Saba, MD, FACP to serve as the confirmatory global Phase III clinical trial Lead, as a member of the Study Steering Committee, for CEL-SCI’s upcoming confirmatory registration study for Multikine in newly diagnosed head and neck cancer (Press release, Cel-Sci, NOV 13, 2024, View Source [SID1234648263]).

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Dr. Saba is a nationally and internationally recognized expert in head and neck cancer and is professor and vice chair in the Department of Hematology and Medical Oncology at Emory University School of Medicine, and the Inaugural Lynne and Howard Halpern Chair in Head and Neck Cancer Research at Emory University School of Medicine. He holds a joint appointment as professor in the Department of Otolaryngology at Emory University School of Medicine. He serves as director of the Head and Neck Cancer Medical Oncology Program and is co-leader of the Multidisciplinary Head and Neck Program at Winship Cancer Institute of Emory University.

Dr. Saba’s work is focused on translational research and the study and development of novel therapeutic agents and modalities. He has served as principal investigator in more than 50 clinical trials and chairs national as well as investigator initiated multi-institution studies focusing on novel approaches for treating head and neck and esophageal cancer. Dr. Saba has also been instrumental in establishing the head and neck cancer research working group at Winship Cancer Institute and is the contact principal investigator of the Lead Academic Participating Site (LAPS) grant of the NCI’s National Clinical Trials Network (NCTN).

Dr. Saba has been elected for two terms as chair and chair emeritus of the National Cancer Institute’s task force for recurrent metastatic head and neck cancer and chaired the Rare Tumors Task Force of the National Cancer Institute’s Head and Neck Cancer Steering Committee. He is an active member of the NRG Oncology and Eastern Cooperative Oncology Group Head and Neck Cancer Core Committees, and chairs two NCI cooperative group trials in the field of head and neck oncology under the ECOG-ACRIN group. Dr. Saba has received competitive NIH funding investigating novel genomic approaches in HPV related and unrelated OPCA and is the recipient of intramural funding studying this disease. He has published more than 290 peer reviewed manuscripts and textbook chapters and is editor of two textbooks: "Esophageal Cancer: Prevention, Diagnosis and Therapy" published in two editions and "Sino-Nasal and Skull Base Malignancies". He is associate editor of JNCI, and Head Neck and served as a member of the ASCO (Free ASCO Whitepaper) Guidelines Committee.

On November 13, 2024 Pulmatrix ("Pulmatrix") (Nasdaq: PULM), a clinical-stage biopharmaceutical company, reported a merger agreement with Cullgen Inc. ("Cullgen"), a privately-held, clinical-stage biopharmaceutical company applying its proprietary targeted protein degradation uSMITE platform to discover and advance therapeutics for the treatment of cancer and other diseases (Press release, Pulmatrix, NOV 13, 2024, View Source [SID1234648284]). Cullgen utilizes its proprietary technology platform, uSMITE, featuring novel E3 ligands, to build the next generation of targeted protein degraders and degrader-antibody conjugates ("DACs").

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In 2023 Cullgen completed a Series C financing led by AstraZeneca-CICC Venture Capital Partnership, and also announced a strategic partnership with Astellas Pharma Inc.

About the Proposed Transaction

Subject to the terms and conditions of the merger agreement, and upon the closing of the merger, pre-merger Pulmatrix stockholders are expected to own approximately 3.6% of the combined company, and pre-merger Cullgen stockholders are expected to own approximately 96.4% of the combined company which will operate under the name Cullgen Inc., be headquartered in San Diego, CA and trade on The Nasdaq Capital Market (Nasdaq). Pulmatrix stockholders will also receive a special cash dividend to the extent that Pulmatrix’s net cash at closing exceeds $2.5 million, subject to certain adjustments.

The transaction is expected to close by the end of March 2025, subject to obtaining stockholder and CSRC approval.

Management and Board of Directors

At the effective time of the merger, the executive officers of the combined company will be led by Ying Luo, Ph.D. Cullgen’s Chairman and CEO. The Cullgen Board of Directors will be supplemented by one representative of Pulmatrix.

Ying Luo, Ph.D., commented, "I’m delighted to announce this planned merger with Pulmatrix, which comes at a pivotal moment in the evolution of our company as we advance our pipeline of targeted protein degraders into clinical development for cancer and other diseases. Listing on Nasdaq will help fuel our growth and enable us to unlock the full potential of our technology platform, including our plans to develop and advance degrader-antibody conjugates and additional targeted protein degraders into the clinic."

Peter Ludlum, Interim Chief Executive Officer of Pulmatrix, added, "Following a thorough evaluation of strategic alternatives, the Pulmatrix board of directors and management team believe that this anticipated transaction represents an opportunity to deliver value to our stockholders. We anticipate that this merger will allow our stockholders to participate in Cullgen’s promising research and development activities and also provide a benefit in the form of a potential dividend component immediately prior to the close of the merger. Prior to transaction closing, we will attempt to increase cash available for the special dividend by divesting corporate assets including PUR1800, PUR3100, and the patent portfolio for iSPERSE."

Cullgen Pipeline Overview and Development Milestones

Cullgen currently has three degrader programs that are in or about to initiate Phase 1 clinical testing. CG001419 is a first-in-class, selective, clinically active, oral pan-TRK degrader that is being studied in two separate clinical trials—one for solid tumors, and the other for the treatment of acute and chronic pain. With respect to the cancer trial, Cullgen has dosed ten patients thus far with no observed dose-limiting toxicity, treatment-related serious adverse events or grade ≥ 3 treatment related adverse events. Regarding the pain trial, Cullgen recently received HREC (Australia) approval to begin enrolling patients to evaluate the safety and pharmacokinetic characteristics of CG001419 in healthy volunteers. Cullgen anticipates enrolling the first patient in early 2025. This program aims to provide a new non-opioid non-NSAID analgesic which can fulfill unmet medical needs in the field of pain.

Cullgen is also evaluating CG009301, a GSPT1 degrader for the treatment of blood cancers including relapsed/refractory acute myeloid leukemia (AML), higher-risk myelodysplastic syndrome (HR-MDS), and acute lymphoblastic leukemia (ALL). Cullgen has received IND allowance from the China CDE for this product candidate and Cullgen anticipates dosing the first patient in the first quarter of 2025. CG009301 also has the potential to be used for the treatment of solid tumors harboring MYC amplification.

In addition to these three clinical programs, Cullgen is also advancing several other targeted protein degraders and DACs, predominantly for the treatment of cancer and autoimmune disease, including a program targeting a cell cycle protein that has been partnered with Astellas Pharma Inc.

Webcast Information

Management will host an informational webcast that will be made available to access at 12:00 pm ET today. A link to the webcast can be found in the Investor Events and Presentations section of the Pulmatrix website at and in the News & Events section of Cullgen’s website at .