On August 18, 2021 Sutro Biopharma, Inc. (NASDAQ: STRO), a clinical-stage drug discovery, development and manufacturing company focused on the application of precise protein engineering and rational design to create next-generation cancer and autoimmune therapeutics, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for STRO-002, a folate receptor alpha (FolRα)-targeting antibody-drug conjugate (ADC), for the treatment of patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received one to three prior lines of systemic therapy (Press release, Sutro Biopharma, AUG 18, 2021, View Source [SID1234586733]).

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"We are pleased with the FDA’s decision to grant Fast Track designation for STRO-002 and welcome the opportunity to have more frequent interactions with the agency," said Dr. Arturo Molina, Chief Medical Officer of Sutro Biopharma. "We continue to be enthused by the potential of the STRO-002 program, which has shown encouraging preliminary activity and tolerability in our Phase 1 dose-escalation study in ovarian cancer, and plan to continue to work with the FDA to potentially accelerate our clinical and regulatory efforts."

Bill Newell, Chief Executive Officer of Sutro Biopharma added, "Receiving Fast Track designation is an important recognition for STRO-002 as a potentially best-in-class FolRα ADC for women with ovarian cancer. We look forward to further collaboration with the FDA to bring this potentially important therapeutic option to women in advanced stages of their disease with limited treatment options."

About Fast Track Designation

The FDA’s Fast Track designation is intended to facilitate the development and review of drug candidates that treat serious conditions or life-threatening conditions and demonstrate the potential to address an unmet medical need. A drug candidate that receives Fast Track designation can expect more frequent interaction with the FDA to discuss the drug candidate’s development plan, the potential for accelerated approval, and the possibility of priority review, if relevant criteria are met at the time of submission of a Biologic Licensing Application (BLA).

About STRO-002 Clinical Development

STRO-001-GM1 is a Phase 1 trial for STRO-002 for patients with advanced ovarian cancer that have progressed or relapsed after standard of care treatments, to assess efficacy, safety, and tolerability. The dose-escalation cohort has been completed and the dose-expansion cohort has enrolled patients from sites in the U.S. and in Spain, with enrollment ongoing. Patients are not pre-selected for FolRα expression but are required to provide a tissue sample for FolRα analysis prior to study treatment. Patients are randomized 1:1 and treated with STRO-002 at either 4.3 or 5.2 mg/kg every three weeks.

On August 18, 2021 Senhwa Biosciences, Inc. (TPEx: 6492), a drug development company focused on first-in-class therapeutics for oncology, rare diseases, and novel coronaviruses, reported that the US Food and Drug Administration (FDA) has granted Fast Track Designation for Silmitasertib, a highly selective inhibitor of casein kinase 2 (CK2) to treat patients with recurrent sonic hedgehog (SHH) driven Medulloblastoma (Press release, Senhwa Biosciences, AUG 18, 2021, View Source [SID1234586732]).

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Fast Track Designation expedites the review of new drugs for serious conditions currently without effective treatments. Through Fast Track, Senhwa is eligible to apply for Accelerated Approval and Priority Review upon reaching relevant criteria with the US FDA. "We are delighted to receive Fast Track Designation and look forward to working closely with the FDA to accelerate the development of Silmitasertib, aiming to promptly bring a meaningful treatment to patients with recurrent SHH driven Medulloblastoma," said Tai-Sen Soong, Chief Executive Officer of Senhwa Biosciences.

Senhwa’s clinical partner, the Pediatric Brain Tumor Consortium (PBTC, www.pbtc.org), is currently conducting a Phase I/II and Surgical Study of Silmitasertib in both children and adults with recurrent SHH Medulloblastoma. This study is taking place at the PBTC’s participating member academic medical centers and children’s hospitals across the United States. The PBTC is sponsoring this clinical trial and is funded through the Consortium grant awarded by the US National Institute of Health – Cancer Therapy Evaluation Program (CTEP).

Medulloblastoma is the most common cancerous brain tumor in children, but no targeted therapy is currently available. On July 6, 2020, Silmitasertib was also granted Rare Pediatric Disease (RPD) Designation from the US FDA. If certain criteria are met with the RPD Designation, Senhwa is eligible for a transferrable Priority Review Voucher (PRV). The PRV allows its recipient an expedited review process of any one of its new drug products from a ten-month to a six-month timeframe.

About Silmitasertib

Silmitasertib is a first-in-class small molecule drug that targets the CK2 (casein kinase 2) pathway and acts as a CK2-inhibitor. It is safe and well-tolerated in humans and is easily administered due to its oral formulation. A Phase II Investigator-Initiated Trial (IIT) for the treatment of moderate COVID-19 recently completed enrollment, and another Phase II IIT to treat severe COVID-19 patients is currently enrolling patients in the United States. Silmitasertib is also being provided under compassionate use for patients with severe COVID-19 in Taiwan (initiated in June 2021).

In addition to COVID-19, Silmitasertib is currently under development in several oncology programs in adults and children with recurrent/advanced or metastatic cancer. To date, three Phase I trials and one Phase II trial of Silmitasertib in cancer patients have been completed; currently, there are two ongoing Phase II studies of Silmitasertib in cancer patients. US FDA granted Silmitasertib an Orphan Drug Designation for the treatment of Cholangiocarcinoma in December 2016 and a Rare Pediatric Disease Drug Designation for the treatment of Medulloblastoma in July 2020.

On August 18, 2021 National Institute for Health and Care Excellence (NICE) reported that Endomag’s lymphatic tracer, Magtrace, that it has received a positive Medtech Innovation Briefing (MIB) from the National Institute for Health and Care Excellence (NICE) locating sentinel lymph nodes (Press release, NICE, AUG 18, 2021, View Source [SID1234586731]). The magnetic liquid is the first and only tracer to receive this positive endorsement and allows any patient or hospital to access the highest standard in breast cancer staging, without the need for nuclear facilities or radioisotopes.

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NICE’s positive review is a national mark of excellence, informing local NHS planning and decision-makers how to provide better patient care. It was published as part of a Medtech Innovation Briefing commissioned by NHS England in support of the NHS 5-Year Forward View, to accelerate innovation in new treatments and diagnostics.

To determine if breast cancer has spread, doctors analyse the "sentinel", or nearest, lymph nodes to the tumour to see if they contain cancer cells. Magtrace helps doctors mark these sentinel nodes by emitting a magnetic signal to guide them to the site of the nodes. Its tiny magnetic particles quickly pass through the lymphatic system and follow the same path a spreading cancer cell would take. It can be injected any time between 20 minutes and 30 days ahead of a sentinel lymph node biopsy, reducing the patients’ time in hospital and enabling the more efficient use of NHS resources.

Commonly, a radioactive isotope, technetium-99m, and blue dye is used to mark sentinel lymph nodes for biopsy. However, when the UK left the European Union in January 2020, it also left Euratom, a commissioning body which governs the use and transport of radioactive material like technetium-99m. Subsequent delays have resulted in some NHS hospitals staging breast cancer with just blue dye, associated with a high false negative rate of 13%, as well as a risk of allergic reaction, or anaphylaxis.2,3

"A sentinel lymph node biopsy is the standard of care for staging early breast cancer and is vital in helping us understand whether cancer has spread," explains Kate Williams, Consultant Oncoplastic Breast Surgeon at North Manchester General Hospital, Manchester Foundation Trust, and one of the experts that contributed to Magtrace’s NICE’s briefing. "It’s concerning to hear that women with breast cancer are having this procedure with substandard techniques when there are non-radioactive alternatives like Magtrace, ready and available."

Unlike technetium-99m, the Magtrace lymphatic tracer is manufactured in the UK and requires no nuclear facilities to be stored or used. It is also well-tolerated and carries no risk of allergic reactions.3 As the UK Government works to address the cancer backlog seen as a result of the pandemic, and to fulfil its promise to ‘level-up’ its commitment to UK science and technology, Endomag’s Magtrace could play a vital role in supporting the healthcare system to tackle the challenges seen with the current standard of breast cancer care.

"Breast cancer is better understood than any other cancer today. And yet, the need for innovation has never been greater, as so many patients have been missed during the pandemic. We feel more determined than ever to make a difference after this NICE positive review, which confirms that innovative UK technologies like the Magtrace marker can play a role to help the health system continue staging breast cancer," said Eric Mayes, CEO, Endomag.

To compile its Medtech Innovation Briefing, NICE obtained feedback from clinical experts who all agreed that the Magtrace lymphatic tracer’s magnetic mechanism of action was a key innovative feature. Magtrace has been shown to be non-inferior to technetium-99m and blue dye in numerous clinical trials involving over 5,000 patients.

In total, over 160,000 women across more than 600 hospitals in 40 countries have already been able to access more precise and less invasive breast cancer treatment thanks to Endomag’s technologies. Endomag welcomes NICE’s positive review of the Magtrace lymphatic tracer and will continue to work to support access and improve standards of care for all breast cancer patients.

On August 18, 2021 IASO Biotherapeutics (IASO Bio), a clinical-stage biopharmaceutical company advancing the development of novel cell therapies for cancer, reported that the preclinical results of the company’s proprietary next-generation chimeric antigen receptor (CAR)-T cell therapy, CT125A, were recently published in Molecular Therapy, an internationally renowned peer-reviewed scientific journal (Press release, IASO Biotherapeutics, AUG 18, 2021, View Source [SID1234586730]). CT125A is a novel first-in-class CAR-T therapy and a groundbreaking asset developed on IASO Bio’s fully human antibody platform IMARS for the treatment of T cell hematologic malignancies.

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Molecular Therapy is the official periodical of the American Society of Gene & Cell Therapy, and is published under Cell. With an impact factor of 11.454 in 2021, Molecular Therapy is dedicated to publishing peer-reviewed and cutting-edge reviews and commentaries, for promoting the sciences in genetics, medicine, and biotechnology. The published study was jointly carried out by IASO Bio and the research team led by Prof. Jianfeng Zhou at Tongji Hospital of Huazhong University of Science and Technology’s Tongji Medical School. Dr. Zhenyu Dai and Dr. Wei Mu of IASO Bio are the co-first authors of the paper, and Dr. Taochao Tan, Executive Director of R&D at IASO Bio, is the program lead in charge of the preclinical development of CT125A.

Study highlight: a new strategy for treatment of T cell malignancies

Researchers of the study successfully selected CD5-targeting fully human heavy-chain variable (FHVH) domains from a phage display library, and knocked out CD5 from those T cells using CRISPR/Cas9 technology, overcoming self-activation and fratricide problems on CAR-T cells. A series of in vivo and in vitro functional comparisons validated the hypothesis that tandem VH domains targeting different epitopes could potentially enhance the function of CAR-T cells, and CT125A, with its biepitopic FHVH3/VH1 CAR-T cells, offers a promising new strategy for the treatment of T cell malignancies.

CD5: a novel and safe target for the treatment of T cell malignancies

In recent years, CAR-T technology has seen numerous breakthroughs and achieved tremendous progress with the development of targets for the treatment B cell malignancies. However, the research and application of CAR-T technology in the treatment of T cell malignancies thus far remains limited. T cell malignancies include T cell acute lymphoblastic leukemia (T-ALL) and T cell lymphoma (TCL)1. CD5 overexpression occurs in approximately 85% of all T cell malignancies, while CD5 expression in normal human cells only occurs in thymocytes, T cells, and B1 cells. CD5 is also expressed in certain B cell malignancies, making CD5 a valid target for the treatment of both T cell and B cell malignancies. At present, only a handful of CD5-targeting therapies are in development, and all of these programs are at early stages.

A groundbreaking biepitopic: CAR-T with fully human heavy-chain-only binding domains offers more potent and durable antitumor activity with lower immunogenicity. The study used IASO Bio’s in-house developed fully human phage display antibody library IMARS to generate antibodies that specifically bind to the CD5 antigen (including scFv and VH only domains), developed CAR-T cells using CD5-specific antibodies, and subsequently compared the function of candidate CAR molecules. To eliminate the adverse effects of fratricide on CAR-T cells, researchers performed CRISPR/Cas9-based CD5 knockout on the T cells, and further developed and optimized the cell-generating process that delivered the high CD5 knockout efficiency and high-quality generation of CAR-T cells. Based on this process, researchers generated clones that exhibited both superior antitumor activity and significantly higher proliferation than the control CAR (H65) in vivo.

Through a competitive analysis, researchers identified FHVH1 and FHVH3 domains that specifically bind to different epitopes of CD5. To further enhance the function of CAR-T cells and minimize the risk of tumor escape due to the mutation and down-regulated expression of the CD5 antigen, researchers further developed and optimized the structural arrangement of tandem VH CARs. Compared to FHVH1, FHVH3, and H65 CAR-T controls, biepitopic FHVH3/VH1 CAR-T cells demonstrated higher levels of degranulation and cytotoxicity in CD5+ cells, including the cell lines with relatively low levels of CD5 expression. In murine-derived tumor models, biepitopic FHVH3/VH1 CAR-T cells cleared T-ALL cells earlier than FHVH1 and FHVH3 CAR-T cells and maintained a longer remission than FHVH1 and FHVH3 CAR-T cells. This finding indicates the more potent and durable antitumor activity of biepitopic FHVH3/VH1 CAR-T cells.

CT125A: a promising new therapy that could bring hope to patients with T cell malignancies

Compared to patients with B cell malignancies, those with T cell malignancies treated with radiochemotherapies have a higher rate of relapse and poorer prognoses, thus representing an urgent unmet clinical need. CT125A is an innovative first-in-class CAR-T therapy that could potentially bring hope to patients with relapsed/refractory T cell malignancies. Furthermore, CD5 is also commonly overexpressed in some hard-to-treat B cell malignancies such as B cell chronic lymphocytic leukemia (B-CLL) and mantle cell lymphoma (MCL), suggesting therapeutic utility in an even broader spectrum of hematologic indications.

"Due to the high relapse rates and dismal prognoses after radiochemotherapies, T cell malignancies remain a hard-to-treat subtype of hematologic malignancies with an urgent need for effective treatment options," said Dr. Biao Zheng, Chief Scientific Officer of IASO Bio. "CT125A is developed using a gene editing technology that delivers CD5 knockout in T cells to prevent the self-activation and fratricide of CAR-T cells. It also leverages CD5-targeting fully human heavy-chain-only binding domains that regulate the development of antibodies. Thus, CT125A can effectively address the high relapse rate of T cell malignancies caused by the lack of in vivo persistence of CD5-targeting CAR-T cells."

Results from this study showed that CD5-targeting CAR-T cells are safe and have potent clinical activity in patients with r/r CD5+ T-ALL or T cell non-Hodgkin lymphoma (T-NHL), and could potentially allow patients who are ineligible for transplants to finally receive hematopoietic stem cell transplantation (HSCT). As CD5 is also commonly overexpressed in certain B cell malignancies, this CAR-T candidate also has clinical utility in patients with B cell malignancies such as mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL). Furthermore, the application of CAR-T therapy to target two or more antigens simultaneously is an attractive strategy for treatment and prevention of antigen-loss relapses. Using two VH domains can simplify the design of bispecific CAR constructs, and is therefore an effective approach to solving critical problems in cancer drug development, such as clonal heterogeneity and antigen escape.

CT125A is currently undergoing chemistry, manufacturing, and control (CMC) studies, as well as an investigator initiated clinical trial (ClinicalTrials.gov identifier: NCT04767308).

On August 18, 2021 Ranok Therapeutics (Hangzhou) Co. Ltd., an emerging biopharmaceutical company focused on developing breakthrough therapies for cancer and other serious diseases, reported it had secured a $40 million Series B funding round denominated in both U.S. dollars and Chinese yuan (Press release, Ranok Therapeutics, AUG 18, 2021, View Source [SID1234586729]). The financing was led by Lapam Capital and Shanghai Healthcare Capital, with additional participation from Wu Capital, Zhongguancun Kaiyuan Capital and existing investors, and representatives of the new investors will join Ranok’s expanded board of directors. To date, Ranok has raised the equivalent of over $50 million in funding.

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Ranok has developed a proprietary and innovative targeted protein degradation (TPD) platform technology, CHAMP (Chaperone-mediated Protein Degradation), that leverages Ranok’s founders’ expertise in protein homeostasis to take advantage of the cellular chaperome network, potentially improving drug safety and efficacy due to selective targeting of disease tissues.

"We are delighted by the enthusiastic response from investors to this financing, which is a strong endorsement of Ranok’s strategic vision and research programs," said Weiwen Ying, Ph.D., Founder and Chief Executive Officer of Ranok Therapeutics. "These funds will enable us to advance our first cancer therapy into clinical trials in the near future and continue to progress our pipeline of novel CHAMP targeted protein degraders. We believe our approach may provide important benefits both in safety and in efficacy for areas of significant unmet need. We welcome our new investors and greatly appreciate the continued support of our existing investors."

"We are very optimistic about the direction and opportunity of the emerging field of TPD and its application to traditionally undruggable disease targets. Ranok’s founders, who bring decades of experience in protein degradation, have developed a unique technology platform that is highly differentiated from competing degrader approaches. We are delighted to work with innovative companies such as Ranok and look forward to helping quickly and efficiently bring their novel medicines to patients," said Zhihua Yu, Chairman of Lapam Capital.

"TPD is an exciting new paradigm in drug development, and Ranok’s CHAMP technology has unique advantages in comparison to other protein degrader approaches, such as PROTAC," said Hong Wen, Ph.D., Partner at Shanghai Healthcare Capital. "We share Ranok’s vision to become a leading protein degradation therapy company with a global impact by creating breakthrough medicines for patients suffering from cancer and other diseases."

The Series B financing proceeds will support continued development of Ranok’s most advanced cancer program, which is expected to be announced by the end of 2021, as well as expansion of its preclinical pipeline of novel therapies based on the proprietary CHAMP technology platform.