On October 18, 2022 Ambrx Biopharma Inc., or Ambrx, (NYSE: AMAM), a clinical stage biopharmaceutical company using an expanded genetic code technology platform to create Engineered Precision Biologics (EPBs), reported a strategic reprioritization of its pipeline and provided a corporate update (Press release, Ambrx, OCT 18, 2022, View Source [SID1234622178]). The strategic assessment considered the company’s cash runway, pipeline near term value creation opportunities, and other factors. As part of this strategic update, Ambrx will streamline its organization to improve efficiency and reprioritize its development pipeline to focus on oncology assets with the greatest potential and strong competitive profiles.

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"The tough decisions we are announcing today will streamline Ambrx’s operations and provide us with the resources to pursue our development candidates that hold the greatest promise for success in people with cancer," said Kate Hermans, Interim Chief Executive Officer of Ambrx. "There has been a significant shift this past year in the HER2 metastatic breast cancer competitive landscape. As a result of our assessment, the Board has endorsed the decision that the company should pause the internal development of ARX788 and seek a partner to further its development ex-China in order to extend the cash runway into 2025. Ambrx will focus on strengthening its current partnerships, while forging new collaborations to progress both ARX788 and other pipeline assets, in various indications. In parallel, we will concentrate our internal development on earlier stage programs where we believe Ambrx offers a first-in-class or best-in-class approach, including our now lead candidate ARX517, which has the potential to be the first Prostate-Specific Membrane Antigen (PSMA)-targeting ADC."

Ms. Hermans continued, "As a result of today’s reprioritization, management expects Ambrx now has sufficient capital to fund operations into 2025. We believe these changes position Ambrx for future success and reflect both our confidence in the company’s EPB platform and our commitment to building shareholder value. We look forward to executing on this new strategy and providing further updates in due course."

"I am pleased that the Board and management of Ambrx have aligned on a strategic path forward as we navigate through the highly competitive oncology market," said Katrin Rupalla, Chair of Ambrx’s Board of Directors. "We believe that prioritizing our play-to-win ADC assets will put Ambrx in the best position to maximize shareholder value and improve the lives of people with cancer. I would like to thank all our employees and partners for their hard work, patience and tenacity as we work through these changes and toward an encouraging future for our patients and stakeholders."

Pipeline Update

In mid-August 2022, Ambrx announced that it would undertake a strategic review of its clinical development pipeline. Moving forward, the company plans to focus on leveraging its novel antibody-engineering technology to target cancer indications. Specifically, Ambrx has developed a proprietary, site-specific conjugation platform that provides homogenous ADCs with unmatched stability. With a narrower scope, Ambrx believes it is better positioned to progress future ADC assets.

Ambrx will prioritize the progression of ARX517 through the clinic as the company’s new lead asset. The company believes ARX517 has the potential to be the first ADC therapy that specifically targets Prostate Specific Membrane Antigen (PSMA) to treat prostate cancer. Prostate cancer represents a significant unmet medical need with 1.4 million new cases worldwide in 2020, representing an estimated $9.9 billion market. In August 2021, Ambrx announced the first patient was dosed with ARX517 in a Phase 1a clinical trial in subjects with PSMA-expressing tumors.

Due to changes in the HER2 competitive landscape, Ambrx will no longer directly pursue our anti-HER2 antibody-drug conjugate (ADC) asset ARX788 as its lead clinical asset. As such, the company will pause development of Ambrx-sponsored clinical trials involving ARX788. Instead, Ambrx will continue to work collaboratively with NovoCodex and seek a development partner(s) ex-China to progress ARX788.

Ambrx highly values its global partners and plans to continue working collaboratively with NovoCodex (ARX788, ARX305), Sino Biopharm (ARX102) and BeiGene (research collaboration).

Additional pipeline programs, ARX305 (anti-CD70 ADC) and ARX102 (smart PEG-IL2), will continue in development. The two assets align with Ambrx’s new development strategy of focusing on early-stage EPBs. Ambrx will leverage clinical data from its partners who are progressing the two assets to inform Ambrx-sponsored clinical trials.
Anticipated Near Term Pipeline Milestones

2H 2023: Ambrx sponsored globally (U.S.) Interim Phase 1a safety data for ARX517, leading to a recommended dose that would allow Ambrx to initiate a Phase 1b/2 trial

2H 2023: Initiation of Ambrx sponsored globally (U.S.) Phase 1a trial for ARX305 (subject to results from NovoCodex sponsored trial)

1H 2024: IND submission for ARX102 (subject to results from Sino Biopharm sponsored trial)
Corporate Update

Ambrx will streamline its organization to reflect its new pipeline development focus. The company will reduce its workforce by approximately 15% while retaining and attracting key talent to support the clinical development of ARX517 and other assets.

The company’s search for a permanent Chief Executive Officer to lead Ambrx is ongoing. Until a permanent CEO is designated, Kate Hermans will continue to serve as interim CEO overseeing the company’s new strategy.

Ambrx expects its cash, cash equivalents and marketable securities as of June 30, 2022 to fund operations into 2025.
Conference Call

Ambrx will host a webcast to discuss the corporate update today, October 18, 2022 at 5:00 p.m. EST / 2:00 p.m. PST. Individuals interested in listening to the conference call may do so by accessing the webcast link in the investor relations section of the company’s website: www.ambrx.com. To access the call by phone, please refer to the dial in details provided in the event page on the "Events and Presentations" page on the investor relations website.

On October 18, 2022 Scopus BioPharma Inc. (Nasdaq: "SCPS"), a biopharmaceutical company developing transformational therapeutics for serious diseases with significant unmet medical need, reported the completion of a series of related recapitalization transactions designed to enhance shareholder value (Press release, Scopus BioPharma, OCT 18, 2022, View Source [SID1234622165]).

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These transactions include the elimination of warrants to purchase approximately 21 million shares of Scopus common stock. The recapitalization also independently values Duet BioTherapeutics, Scopus’ pure play immuno-oncology subsidiary, at $25 million.

Joshua R. Lamstein, Chairman of Scopus BioPharma, stated, "Highlighting the embedded value of Duet was a key driver for the recapitalization. Scopus retains an approximately 90% ownership stake in Duet. The value of this stake greatly exceeds the total current market capitalization of Scopus. We expect that completing the recapitalization should serve as a catalyst for a significant increase in the trading price of Scopus’ common stock."

Alan Horsager, Ph.D., President – Immuno-Oncology of Scopus BioPharma and President and Chief Executive Officer of Duet BioTherapeutics, stated, "The establishment of a $25 million independent, stand-alone valuation positions Duet to raise capital directly and go public in 2023."

Mr. Lamstein added, "The recapitalization transactions provide us with greater strategic flexibility. The opportunity to secure capital at both the Scopus and Duet corporate levels enables us to pursue the most attractive financing alternatives."

Dr. Horsager added, "The additional financing alternatives afforded to Duet will enhance our access to the capital necessary to accelerate the development of DUET-02, our highly promising antisense technology. Additional capital resources will also enable us to further the on-going research by Marcin Kortylewski, Ph.D., Co-Founder and Senior Scientific Advisor of Duet BioTherapeutics and Professor of Immuno-Oncology at City of Hope, into systemic delivery formulations for DUET-01. We believe that these advancements will enable Duet to go public at a valuation significantly in excess of its current $25 million valuation."

On October 18, 2022 Vect-Horus reported that Great occasion to assist to valuable conferences about Nuclear Medicine, Molecular Imaging, Optimization of Radiolabeled Biomolecules in one of the most valuable Nuclear Medicine event in Europe (Presentation, Vect-Horus, OCT 18, 2022, View Source [SID1234622163]).
Meet with Cedric Malicet, PhD during the EANM on Oct 15-19, 2022 in Barcelona.

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On October 18, 2022 ViewRay, Inc. (NASDAQ: VRAY) reported the launch of a phase III randomized controlled trial titled "Locally Advanced Pancreatic cancer treated with ABLAtivE stereotactic MRI-guided adaptive radiation therapy" – also known as LAP-ABLATE (Press release, ViewRay, OCT 18, 2022, View Source [SID1234622159]). LAP-ABLATE will compare stand-alone multi-agent chemotherapy, which is the current standard of care for patients with locally advanced pancreatic cancer, to patients receiving a combination of chemotherapy and 5-fraction MRIdian SMART (stereotactic MR-guided adaptive radiotherapy). The study is designed to demonstrate superior overall survival in patients receiving post-chemotherapy MRIdian SMART. The anticipated enrollment target is 267 patients (NCT05585554).

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Although surgery is considered a potentially curative treatment for non-metastatic pancreatic cancer, less than 20 percent of patients are candidates. Of the remaining patients, approximately 40 percent have locally advanced pancreatic cancer (LAPC), and another 40 percent have distant metastases at diagnosis. LAPC is usually not resectable because the tumor encases major abdominal blood vessels.

"This first-of-its-kind prospective multi-center international randomized controlled trial was prompted by the exciting results of several recently published ablative MRIdian SMART studies that demonstrated markedly improved treatment efficacy and reduced toxicity compared to outcomes from non-ablative radiation therapy," said Michael D. Chuong, M.D., lead investigator of the LAP-ABLATE trial and Medical Director of Radiation Oncology at the Miami Cancer Institute, part of Baptist Health South Florida. "While prior studies of chemotherapy plus non-ablative radiation have not shown an improvement over chemotherapy alone for patients with LAPC, we believe MRIdian’s advanced capabilities overcome the many limitations of other radiation treatment modalities. Ablative doses with MRIdian SMART can provide pancreatic cancer patients a clinically meaningful improvement in long-term survival while maintaining an excellent quality of life and rarely causing significant side effects."

Conventional chemotherapy plus non-ablative radiotherapy has not demonstrated improvements to overall survival. Further studies have supported the notion that significantly escalating the radiation dose to an ablative range may improve overall survival. But the feasibility of delivering ablative radiation dose to the pancreas has historically been limited. Previous clinical trials have resulted in a high risk of injury to the stomach and nearby bowel loops, resulting in severe side effects such as pain, bleeding, or obstruction.

"Pancreatic cancer is one of the most challenging diseases to treat, and while currently available therapies can have a meaningful impact for a proportion of patients, they are non-curative for the vast majority," said Martin Fuss, M.D., Chief Medical Officer at ViewRay. "LAP-ABLATE will evaluate the combination of chemotherapy and MRI-guided ablative dose radiation therapy to determine MRIdian’s role in improving overall survival outcomes and expanding the treatment options for patients with locally advanced disease."

MRIdian integrates MRI technology, radiation delivery, and proprietary software to locate, target, and track soft-tissue and tumors. By providing real-time continuous tracking of the tumor and organs-at-risk, MRIdian enables automatic gating of the radiation, turning the beam off if the target moves outside user-defined margins. This allows for precise delivery of the prescribed dose to the target while sparing surrounding healthy tissue and critical structures.

"Despite major advances in other oncology indications, treatment options for pancreatic cancer remain severely limited, including for patients with locally advanced disease," said Julie Fleshman, President and CEO of the Pancreatic Cancer Action Network (PanCAN). "At PanCAN we support patient involvement in clinical trials as a way to gain access to some of the best treatment options and most cutting-edge approaches. We’re looking forward to the results of the LAP-ABLATE trial and the opportunity to validate a potential breakthrough therapy for this group of patients."

To date, over 25,000 patients have been treated with MRIdian. Currently, 54 MRIdian systems are installed at hospitals around the world where they are used to treat a wide variety of solid tumors and are the focus of numerous ongoing research efforts. MRIdian has been the subject of hundreds of peer-reviewed publications, scientific meeting abstracts, and presentations. For a list of treatment centers, please visit: View Source

On October 18, 2022 CARsgen Therapeutics Holdings Limited (Stock Code: 2171.HK), a company focused on innovative CAR T-cell therapies for the treatment of hematologic malignancies and solid tumors, reported that the National Medical Products Administration (NMPA) of China has accepted the New Drug Application (NDA) for zevorcabtagene autoleucel ("zevor-cel," R&D code: CT053), a fully human, autologous BCMA CAR T-cell therapy for the treatment of relapsed and/or refractory multiple myeloma (R/R MM) (Press release, Carsgen Therapeutics, OCT 18, 2022, View Source [SID1234622158]).

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The acceptance of the NDA is based on data from an open-label, single arm Phase I/II clinical trial (LUMMICAR STUDY 1 [Protocol number CT053-MM-01]) in China. Study results showed that zevor-cel has excellent safety and efficacy profiles. Zevor-cel also represents a promising treatment option for patients with high-risk disease.

Multiple myeloma is a fatal blood cancer in which plasma cells found in bone marrow grow out of control and create abnormal proteins that can damage vital organs, including heart and kidneys.[1] According to the World Health Organization, there were more than 21,000 new cases and nearly 16,200 deaths caused by multiple myeloma estimated in China in 2020. [2] With patient survival averaging longer than five years, there were an estimated 113,000 prevalent patients with multiple myeloma including those with newly diagnosed and refractory/relapsed disease in China during the same period. Frost & Sullivan have forecasted that through the 2020s, this prevalence will continue to increase 8-10% each year. [3] Although patients may achieve remission with traditional therapies, most of them experience repeated disease progression. [4] Patients who relapse after traditional therapies, including protease inhibitors, immunomodulatory agents and/or anti-CD38 monoclonal antibodies, have poorer prognoses and few treatment options. [5-6] Therefore, these patients have a substantial clinical unmet need for an efficacious, safe, and convenient treatment.

Prof. Wenming Chen, the principal investigator of the CT053-MM-01 study, Director of Hematology Department, Beijing Chao-Yang Hospital, Capital Medical University, said: "Results from the LUMMICAR-1 study show that the fully human autologous BCMA CAR T-cell product, zevor-cel, demonstrated strong and durable efficacy in patients with relapsed/refractory multiple myeloma, and was generally well tolerated. We are delighted to see that the NDA of this CAR T-cell product with independent intellectual property rights has been officially accepted by the NMPA, and we are looking forward to its early launch and bringing clinical benefits to Chinese patients with relapsed/refractory multiple myeloma."

Prof. Chengcheng Fu, the principal investigator of the CT053-MM-01 study, Director of Hematology Department, the First Affiliated Hospital of Soochow University, said: "In the China confirmatory clinical trial, zevor-cel has shown favorable safety and deep and durable responses in patients with relapsed/refractory multiple myeloma. Excellent patient experience and sufficient scientific evidence have laid a strong foundation for the NDA acceptance. I hope zevor-cel can be approved and launched in China as soon as possible to allow patients early access to this efficacious and safe product."

Dr. Zonghai Li, Founder, Chairman of the Board, Chief Executive Officer, and Chief Scientific Officer of CARsgen Therapeutics, said: "We are delighted that the New Drug Application (NDA) for zevor-cel, a BCMA CAR T-cell fully developed in house by CARsgen, has been accepted by National Medical Products Administration. This milestone cannot be achieved without the joint efforts from CARsgen team, clinical physicians, the strong support from patients and their families, or other partners of CARsgen. I would like to express my cordial thanks to all of them. We look forward to the early approval of zevor-cel to benefit more patients with multiple myeloma. Driven by our vision of ‘Making Cancer Curable’, we will continue to develop more innovative cell therapies for cancer patients."

About Zevor-cel

Zevor-cel (CT053) is a fully human, autologous BCMA CAR T-cell product candidate for the treatment of R/R MM. CARsgen is conducting a Phase 1b/2 clinical trial (LUMMICAR STUDY 2) in North America to evaluate the safety and efficacy of zevor-cel for R/R MM. The Company also plans to conduct additional clinical trials to develop zevor-cel as an earlier line of treatment for multiple myeloma.

Zevor-cel received Regenerative Medicine Advanced Therapy (RMAT) and Orphan Drug designations from the U.S. Food and Drug Administration (FDA) in 2019, as well as the PRIority MEdicines (PRIME) and Orphan Medicinal Product designations from the European Medicines Agency (EMA) in 2019 and 2020, respectively. Zevor-cel also received Breakthrough Therapy designation from the NMPA in 2020.

The Company believes that zevor-cel is well positioned to potentially reshape the treatment paradigm for multiple myeloma and become a foundational treatment for multiple myeloma patients.