On December 14, 2021 AnHeart Therapeutics ("AnHeart"), a clinical-stage global biopharmaceutical group company committed to developing novel precision oncology therapies, reported the completion of a $61 million oversubscribed Series B financing round led by new investor Octagon Capital, with participation from Innovent Biologics, Cenova, Laurion Capital, and Sage Partners (Press release, AnHeart Therapeutics, DEC 14, 2021, View Source [SID1234597125]). The Company has raised a total of $100 million in gross proceeds from private financings since its founding in December 2018.

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The proceeds from the Series B financing will be used to advance the clinical development of AnHeart’s lead asset, taletrectinib, a next-generation ROS1 inhibitor currently in Phase 2 trials in non-small cell lung cancer (NSCLC), and support the continued expansion of its pipeline of precision next-generation oncology therapeutics.

ROS1 oncogenic fusions are observed in approximately 1-2% of or about 20,000 NSCLC patients each year worldwide. ROS1 fusions are also observed in several other cancers such as cholangiocarcinoma, glioblastoma, ovarian, gastric, and colorectal cancers. NTRK fusions are oncogenic driver across multiple advanced solid tumors and observed in more than 90% in very rare cancers such as secretory breast carcinoma, mammary analogue secretory carcinoma of salivary gland and infantile fibrosarcoma, 12.1~14.5% of papillary thyroid cancer and 10.3% of non-brainstem high grade glioma. Incidence of NTRK fusions is below 5% in more common cancers such as lung, breast, melanoma, and colon cancer.

Taletrectinib is a potent, novel, highly selective, next-generation ROS1/NTRK inhibitor for solid tumors with ROS1 fusion or NTRK fusion mutations. It can overcome crizotinib resistance and cross the blood-brain barrier. There is currently no FDA approved drug targeting crizotinib resistance mutations. Taletrectinib is currently in China TRUST trial (Taletrectinib ROS1 LUng STudy, NCT04395677), global TRUST II trial (NCT04919811) and the basket trial in NTRK fusion positive solid tumors (NCT04617054). Impressive interim data of the TRUST Phase 2 trial for NSCLC have been published at ASCO (Free ASCO Whitepaper) and CSCO earlier this year.

"AnHeart is delighted to partner with this group of top-tier, leading healthcare investors to advance development of our pipeline of precision oncology therapeutics. We have made tremendous progress since we founded AnHeart in 2018," Junyuan (Jerry) Wang, Ph.D., Co-Founder and Chief Executive Officer of AnHeart Therapeutics. "This financing reflects strong support for our platform, people, and comprehensive development strategy."

"This strong investment group, comprised of both healthcare specialist funds and a leading biopharma company allows us to accelerate development of our unique pipeline of targeted therapies," said Lihua Zheng, J.D., Ph.D., Co-Founder and Chief Business Officer of AnHeart Therapeutics. "The funding will also allow us to continue expanding our team of world-class scientists and researchers focused on bringing game-changing cancer therapeutics to improve patients’ lives."

"We were attracted to AnHeart by the excellent science, experienced management team and broad pipeline of targeted small molecule therapeutics," said Dr. Ting Jia, "TJ", Ph.D., Founder, Octagon Capital, a New York-based healthcare specialist fund active in both private and public markets. "AnHeart’s lead asset taletrectinib is a promising potential new therapeutic in ROS1 fusion-positive lung cancer patients, with impressive preliminary Phase 2 clinical data reported at ASCO (Free ASCO Whitepaper) and CSCO this year. In addition, we see a tremendous opportunity for AnHeart’s pipeline to produce novel, targeted therapies to address significant unmet medical needs across a broad range of difficult-to-treat cancers."

On December 14, 2021 I-Mab (the "Company") (Nasdaq: IMAB), a clinical stage biopharmaceutical company committed to the discovery, development and commercialization of novel biologics, reported interim data from an ongoing clinical trial (NCT03934814) of lemzoparlimab in combination with rituximab (Rituxan) in heavily treated patients with relapsed or refractory non-Hodgkin’s lymphoma (NHL), at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, I-Mab Biopharma, DEC 14, 2021, View Source [SID1234597164]).

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Lemzoparlimab is a novel CD47 antibody that blocks CD47 and SIRPα interaction through a epitope designed to confer red blood cell (RBC) sparing properties. In all clinical trials conducted so far, lemzoparlimab is administered without a priming dose.

"Lemzoparlimab’s initial results show it appears to be safe and well-tolerated in combination with rituximab without the need of a priming dose," said Amitkumar Mehta, MD, Associate Professor and Director of the Lymphoma Program at the University of Alabama at Birmingham and O’Neal Comprehensive Cancer Center at UAB. "This data support further evaluation of lemzoparlimab in combination with rituximab, which is currently ongoing in study in patients with r/r DLBCL and indolent lymphoma."

The preliminary data was generated from nine patients with relapsed and refractory NHL who received at least two prior lines of therapies, with a median of four lines. Lemzoparlimab was safe and well-tolerated at doses of 20 mg/kg and 30 mg/kg weekly, without a priming dose. The maximum tolerated dose (MTD) was not reached. Most treatment-related adverse events (TRAE) were manageable infusion-related reactions (n=4). Among seven efficacy-evaluable patients, four achieved complete response (CR) [1 transformed FL-DLBCL +3 FL], one partial response (PR) of FL were observed (ORR=71%); two reported stable disease (SD); and the disease control rate (DCR) is 100%. Tumor shrinkage was observed in all evaluable patients. The median time to response was 50 days and response lasted from 61 to 236 days. A high level (80% and 90%) of intra-tumoral distribution measured by IHC of tumor biopsy was reached at 20 mg/kg and 30mg/kg weekly.

"We’re encouraged by the interim results reported today. The clinical data of lemzoparlimab further builds our confidence for an innovative therapy that utilizes macrophages against tumors, said Dr. Joan Shen, Chief Executive Officer of I-Mab. "It is very exciting that lemzoparlimab is bringing new hopes to our patients, and we are accelerating its clinical development through international multi-center trials in the U.S. and China."

The ongoing study with 30 mg/kg lemzoparlimab weekly combined with rituximab is being expanded to enroll more patients with relapsed and refractory diffuse large B-cell lymphoma (DLBCL) or indolent lymphoma.

About CD47 and Lemzoparlimab

CD47 is a cell surface protein over-expressed in a wide variety of cancers and can act to protect tumors by delivering a "don’t eat me" signal to otherwise tumor-engulfing macrophages. CD47 antibody blocks this signal and enables macrophages to attack tumor cells. However, development of CD47 antibody as a cancer therapy has been hampered by its hematologic side effects, such as severe anemia, caused by natural binding of CD47 antibody to red blood cells. Scientists at I-Mab have discovered a novel CD47 antibody, lemzoparlimab, that is designed to target tumor cells while exerting a minimal untoward effect on red blood cells.

Multiple clinical studies are ongoing in both the U.S. and China to explore indications in treating both hematologic maliglencies and solid tumors. Lemzoparlimab is being studied in patients with myelodysplastic syndrome (MDS), acute myelocytic leukemia (AML), and advanced solid tumors in combination with chemotherapy and immune checkpoint inhibitors in the U.S. and China. Combined clinical results from these studies will potentially support registrational trials later in China.

In September 2020, I-Mab and AbbVie entered into a global strategic collaboration to develop and commercialize lemzoparlimab. This includes the design and conduct of further clinical trials to evaluate lemzoparlimab in multiple cancers through global and China-specific trials. AbbVie has assumed sponsorship of the U.S. study as of April 2021.

On December 13, 2021 Celularity Inc. (Nasdaq: CELU) ("Celularity") reported that preclinical data on the development of its placental-derived allogeneic genetically modified NK cell therapy program (CYNK-101) and its placenta-derived allogeneic CAR-NK cell therapy program (CAR19-CYNK), respectively (Press release, Celularity, DEC 13, 2021, View Source [SID1234596914]). The Company reported its findings in two poster presentations at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Meeting and Exposition (ASH) (Free ASH Whitepaper) taking place in Atlanta and virtually December 11-14, 2021 .

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Poster no. 2773: "Human Placental CD34+-Derived Natural Killer Cells with High Affinity and Cleavage Resistant CD16 (CYNK-101) in Combination with Daratumumab for Immunotherapy Against CD38 Expressing Hematological Malignancies"

Session name: 703. Cellular Immunotherapies: Basic and Translational: Poster II
Presentation date/time: Sunday, 12 December 2021; 6:00 pm
Room: Georgia World Congress Center, Hall B5
Highlights: CYNK-101 is a cryopreserved, off the shelf, allogeneic NK cell product candidate, overexpressing a high IgG binding affinity, proteinase cleavage resistant, CD16 variant. The results show the synergistic effect of combining CYNK-101 with daratumumab to drive antibody dependent cellular cytotoxicity activity against CD38+ hematological malignancies in vitro and in vivo. In these studies, CYNK-101 was not susceptible to daratumumab-directed fratricide and did not display on-target, off-tumor cytotoxicity, suggesting CYNK-101 may be a unique NK cell platform that preserves innate immune function in the presence of daratumumab.

Poster no. 2779: "Development of CD19 CAR Engineered Human Placental CD34+-Derived Natural Killer Cells (CAR19-CYNK) As an Allogeneic Cancer Immunotherapy"

Session name: 703. Cellular Immunotherapies: Basic and Translational: Poster II
Presentation date/time: Sunday, 12 December 2021; 6:00pm
Room: Georgia World Congress Center, Hall B5
Highlights: The results demonstrate the feasibility and functionality of expressing a Chimeric Antigen Receptor (CAR) directed to CD19 on placental CD34+ derived, cryopreserved, off-the-shelf, allogeneic CYNK cells. The introduction of CAR in the product candidate CAR19-CYNK did not impact performance of CYNK cell manufacture and endowed additional tumor cell killing against resistant lymphoma cell lines in a CD19-dependent manner, when tested both in vitro and in vivo.

On December 13, 2021 Midatech Pharma PLC (AIM: MTPH; Nasdaq: MTP), a drug delivery technology company focused on improving the bio-delivery and biodistribution of medicines, reported that its Investigational New Drug (IND) application for a Phase 1 study of MTX110, a panobinostat complex to be administered by convection enhanced delivery in patients with recurrent glioblastoma multiforme (rGBM), has been cleared by the US FDA (Press release, Midatech Pharma, DEC 13, 2021, View Source [SID1234596931]). The 30-day review period has expired and the IND has been judged safe to proceed. Accordingly, Midatech has initiated preparations for a study start in the first half of 2022.

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Employing the Company’s MidaSolve technology, MTX110 solubilises panobinostat, a histone deacetylase (HDAC) inhibitor currently used in the treatment of multiple myeloma. In a liquid formulation as MTX110, panobinostat can be delivered directly to a patient’s tumour under constant pressure via a catheter system (Convection Enhanced Delivery, or "CED") thereby bypassing the blood-brain barrier and allowing for high drug concentrations and broader drug distribution in and around the tumour while simultaneously minimising systemic toxicity and other side effects. Panobinostat has demonstrated high potency against patient-derived tumour cells in in vitro and in vivo models.

GBM is the most common and aggressive form of brain cancer in adults, usually occurring in the white matter of the cerebrum. Treatments include radiation, surgical resection and chemotherapy although, in almost all cases, tumours recur. There are approximately 2-3/100,000(1) diagnoses of GBM per annum. Survival with standard of care treatment ranges from approximately 13 months in unmethylated MGMT patients to approximately 30 months in highly methylated MGMT patients(2). Glioblastoma is an intractable brain cancer.

The primary objective of the Phase I study will be to assess the safety and tolerability of MTX110 in patients with rGBM. The study is expected to include two clinical centres in the US and to begin recruiting H1 2022.

Dmitry Zamoryakhin, Chief Scientific Officer of Midatech, said:

"Our solubilising technology in combination with a CED system offers the potential to deliver significantly higher doses of panobinostat, a potent HDAC inhibitor, directly to the tumour. Importantly, this targeting approach is designed to limit systemic circulation of drug and therefore toxicity. This signal finding Phase I study could point the way to a new treatment paradigm for this intractable brain cancer."

This announcement contains inside information for the purposes of Article 7 of Regulation (EU) 596/2014 (MAR).

1.American Association of Neurosurgeons

2.Radke et al (2019). Predictive MGMT status in a homogeneous cohort of IDH wildtype glioblastoma patients. Acta Neuropathologica Communications 7:89 Online: View Source org/10.1186/s40478-019-0745-z

On December 13, 2021 Poseida Therapeutics, Inc. (Nasdaq: PSTX), a clinical-stage biopharmaceutical company utilizing proprietary genetic engineering platform technologies to create cell and gene therapeutics with the capacity to cure, reported interim results from its Phase 1/2 PRIME clinical trial of P-BCMA-101 for the treatment of relapsed/refractory multiple myeloma (R/R MM) at the 2021 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Poseida Therapeutics, DEC 13, 2021, View Source [SID1234596958]).

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The results show that P-BCMA-101, a non-viral transposon-based autologous CAR-T, was well tolerated and demonstrated strong anti-tumor activity in advanced, late line R/R MM patients. The learnings from P-BCMA-101 informed the development of the Company’s first allogeneic program, P-BCMA-ALLO1 which is also being evaluated in R/R MM patients. The Company previously announced that it is winding down the P-BCMA-101 autologous program in favor of the allogeneic program, P-BCMA-ALLO1.

"We are encouraged by the outcomes seen from our clinical trial of P-BCMA-101, results that continue to validate our approach and that have informed P-BCMA-ALLO1, our first fully allogeneic CAR-T program for patients with multiple myeloma, as well as our other programs. Our focus is on creating differentiated product candidates with a high percentage of T stem cell memory (Tscm) cells," said Eric Ostertag, M.D., Ph.D., chief executive officer of Poseida Therapeutics. "Looking ahead, we continue to advance P-BCMA-ALLO1 and P-MUC1C-ALLO1 and look forward to presenting data in 2022 for both of these allogeneic programs."

The PRIME trial is a Phase 1/2, open label 3+3 single dose escalation of P-BCMA-101 CAR-T cells. The primary objective of the study is to determine the safety and maximum tolerated dose of P-BCMA-101 based on dose limiting toxicities (DLT), and the key secondary objective is to assess the anti-myeloma effect of the product. The median patient age was 62, with a median time since diagnosis of approximately 5.8 years. Patients were heavily pre-treated, with a median of 7 prior lines of therapy (2-18). As of the data cut-off date of October 15, 2021, a total of 98 patients have been dosed with P-BCMA-101.

The best observed treatment regimen was a combination with rituximab (n=14), with an overall response rate (ORR) of 78%, a VGPR/sCR rate of 43% and 100% overall survival at the time of the data cutoff. Progression free survival was also improved with rituximab, with median overall survival rates not yet reached in several cohorts including the rituximab combination cohorts. Response rates for other cohorts are consistent with results previously reported.

Across the study, no dose-limiting toxicities were observed. 28% of patients developed cytokine release syndrome (CRS) and 7% of patients developed neurotoxicity. None of the patients developed Grade 3 or higher CRS, and 2% of patients developed Grade 3 neurotoxicity. There were no treatment-related deaths among the patient population and no patients needed ICU admission as a result of CAR-T related toxicities. 28 patients were treated on a fully outpatient basis.

"P-BCMA-101 demonstrated strong anti-tumor activity in advanced multiple myeloma patients, and cohorts to date have shown minimal CRS and neurotoxicity, which allows for safe administration in an outpatient environment and combinations with other therapies," said Caitlin Costello, M.D., Associate Clinical Professor of Medicine and member of the Division of Blood and Marrow Transplantation at the University of California, San Diego. "These data indicate that the piggyBac transposon-based platform is an attractive option for allogeneic CAR-T cells, which has led to a first-in-human Phase 1 study."

The Company’s first fully allogeneic CAR-T cell product, P-BCMA-ALLO1 utilizes Poseida’s proprietary piggyBac DNA delivery system and Cas-CLOVER site-specific gene editing system to create an allogeneic product that prevents both graft-vs-host and host-vs-graft diseases and also incorporates a next-generation BCMA binder. P-BCMA-ALLO1 manufacturing involves a proprietary "booster" molecule that allows for numerous doses to be produced from a single manufacturing run, while maintaining desirable Tscm cells, which can reach percentages in the 60-80% range.

The Investigational New Drug (IND) application for P-BCMA-ALLO1 was given a safe to proceed designation by the FDA in August 2021. The Phase 1 study is an open label, dose escalation study following a 3+3 design of dose escalation in subjects with R/R MM. The study will assess the safety and maximum tolerated dose of P-BCMA-ALLO1 based on dose limiting toxicities. Key secondary objectives of the study include the anti-myeloma effect and safety of P-BCMA-ALLO1.