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ImmVira completed the first dosing for Phase II of MVR-T3011 (intratumoral injection) in the U.S. and China

On June 11, 2021 ImmVira reported that in the Phase II Clinical Trials of its leading oncolytic virus product, MVR-T3011* as intratumoral administration (MVR-T3011 IT), ImmVira has completed the first dosing in both China and the U.S. on May 28 2021 and June 11 2021, respectively (Press release, Immvira, JUN 11, 2021, View Source [SID1234583938]).

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MVR-T3011, ImmVira’s proprietary next-generation, genetically modified oncolytic herpes simplex virus ("oHSV"), is developed on a novel virus backbone design driven by ImmVira’s innovative insights in oncolytic viruses and superior gene recombinant technology. The incorporation of two exogenous genes, PD-1 antibody and IL-12, further enhances immune responses. MVR-T3011 is ImmVira’s first pipeline undergoing clinical trial and includes intratumoral administration of MVR-T3011. Phase I clinical trials commenced in China in April 2020 and commenced in the United States and Australia in September 2020. Data collected from these preliminary Phase I clinical studies have demonstrated a favorable safety profile and promising efficacy profile. No dose-limiting toxicities have been observed in participants.

The U.S. Phase IIa portion of the study consists of two parts: (i) MVR-T3011 as a single agent for melanoma and metastatic solid tumors; (ii) MVR-T3011 in combination with pembrolizumab for non-small-cell lung carcinoma. The China Phase IIa (MVR-T3011 as a single agent) study targets head and neck cancer, sarcoma and breast cancer. These multi-center studies cover various indications providing highly efficient and cost-effective clinical development strategy to rapidly advance clinical development for MVR-T3011 across regions.

"Leveraging the OvPENS new drug R&D platform, ImmVira is a pioneer in the field," said Dr. Grace Zhou, Chairwoman of the Board of ImmVira. "ImmVira will make best use of its long-term experience and creative insights in oncolytic virus to construct broader product pipelines and provide effective, innovative and safe single-agent as well as combined oncolytic virotherapies for the anti-tumor market." Professor Bernard Roizman has resigned from as Chairman of the Board in February 2020 due to personal health reason and he has not held any positions in ImmVira and its subsidiaries since then. Dr. Grace Zhou has been appointed as Chairwoman of the Board since February 2020.

* Note: MVR-T3011 is the pipeline designation representing T3011, the product code registered in the US and China for clinical trials.

HiFiBiO Therapeutics Announces Publication in Science Advances of its High-Throughput Functional Screening for Next-Generation Cancer Immunotherapy

On June 11, 2021 HiFiBiO Therapeutics, a multinational biotechnology company with unique expertise in immune modulation and single-cell science, reported a publication in Science Advances with its collaborators at Nankai University, ShanghaiTech University, and Jiao Tong University about the development of a high-throughput droplet-based approach to identify novel antibodies with functional readouts beyond simple binding (Press release, HiFiBiO Therapeutics, JUN 11, 2021, View Source [SID1234583928]). Innovative therapeutics such as bispecific T-cell engager (BiTE) antibodies and agonist antibodies against costimulatory receptors can reach their full potential through such functional screening.

This approach improves upon conventional screening by allowing for the analysis and screening of functional antibodies at the single-cell level with unprecedented throughput, allowing for more diverse candidates and successful hits. To demonstrate the technical capabilities of the platform, researchers successfully identified functional antibodies for CD40 agonism with low frequency (<0.02%) in two rounds of screening. Additionally, the versatility of the system was shown by combining an anti-Her2 x anti-CD3 BiTE antibody library with functional screening, enabling efficient identification of active anti-Her2 x anti-CD3 BiTE antibodies.

"Our single-cell microfluidic platform’s robustness and versatility has enabled the efficient and unbiased discovery of active antibodies with markedly increased throughput and accuracy," said Bingqing Shen, PhD, Director, Antibody Discovery of HiFiBiO Therapeutics. "We look forward to further leveraging our technology towards identification of functional antibodies for agonist and bispecific antibodies to ensure a sustainable pipeline of next generation novel immunotherapies."

"This technology addresses two main bottlenecks plaguing conventional screening methods for novel immunotherapies, namely, candidate functionality and diversity in a high throughput manner," said Professor Zhang, "Functional droplet-based screening enables direct linking of antibody discovery to functional outcomes which could optimize screening efforts significantly and accelerate the antibody drug discovery process. I can envision that the platform can be applied to screening of other types of molecules such as cytokines and to high-throughput analysis of cell-cell interactions. For example, dendritic cells expressing a library of neoantigens are co-encapsulated with tumor-infiltrating T cells to map the pairs of cognate antigens and T cell receptors (TCRs)."

Yingli Pharma Announces a presentation on the Phase 2 clinical trial of linperlisib, a PI3Kδ selective inhibitor, in relapsed or refractory follicular lymphoma at the European Hematology Association 2021 Congress

On June 11, 2021 Shanghai Yingli Pharmaceuticals Ltd (Yingli Pharma), a clinical stage pharmaceutical company providing new therapies for cancer and metabolic diseases, reported the topline data from a clinical trial sponsored by the company at the annual meeting of the European Hematology Association (EHA) (Free EHA Whitepaper) being held June 9-17, 2021 (Press release, Yingli Pharmaceutical, JUN 11, 2021, View Source [SID1234583915]).

The study entitled ‘A Phase 2 study of an oral PI3Kδ inhibitor YY-20394 in patients with relapsed or refractory follicular lymphoma’ will be presented at EHA (Free EHA Whitepaper) by Dr. Lugui Qiu, a lead investigator from Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, Tianjin, China. This is a registration study that enrolled 93 relapsed or refractory Follicular Lymphoma (FL) patients having received 2 or more prior systemic therapies and was conducted at 32 clinical sites in China. Linperlisib was evaluated as a monotherapy for safety, tolerability and efficacy at recommended phase 2 dose of 80 mg once daily. Following a data cutoff on March 15, 2021, the fully enrolled study was analyzed for 89 evaluable patients. The Overall Response Rate (ORR) was 79.5%, with 12.4% Complete Response, 67.4% Partial Response, and 16.1% Stable Disease, combining to achieve a Disease Control Rate of 96.6%. Previously, the Phase 1 study of linperlisib had shown similar preliminary efficacy of 90% ORR in 10 patients with r/r FL. As of the data cutoff for the Phase 2, the median Progression Free Survival was 11.8 months, and the Duration of Response was 12.3 months. Forty seven patients were continuing to receive linperlisib treatment.

Follicular Lymphoma is increasingly harder to treat if patients progress on previous therapies, usually immuno-chemotherapy is a mainstay as a prior treatment. On this study, 65% of the patients had received 3 or more prior systemic treatments, and all patients had previously received rituximab-based therapies.

The safety data from the FL Phase 2 study indicated that linperlisib was generally safe and tolerable with manageable adverse events. Most of the adverse events were Grade 1 and Grade 2. The most common (>5%) treatment related hematologic adverse events of ≥ Grade 3 were neutropenia (15.1%), leukocytopenia (5.4%), lymphocytopenia (5.4%). The most common (>5%) treatment related non-hematologic adverse events of ≥ Grade 3 were pneumonia (15.1%).

Dr. Lugui Qiu, a prinicipal investigator on the study, stated "FL is complicated as the relapsed and refractory patients tend to progress rapidly, requiring aggressive therapies. From the clinical findings with linperlisib treatment of FL patients, we are seeing durable responses for most patients. Patients are in desperate need of effective therapies that target these lymphoma key signaling pathways and therapies that are oral medications, easy for patients to use outside of a clinic."

Dr. Zusheng Xu, General Manager of Yingli Pharma commented "We are excited to be developing Linperlisib for the treatment of lymphomas and solid tumors. Linperlisib is a next-generation PI3Kδ-selective inhibitor. The clinical data suggest that Linperlisib might be a potentially advantageous treatment option for patients. We have applied a linperlisib marketing approval in China in relapsed or refractory FL, based on the data from this phase II registration study. We hope to broaden the use of linperlisib and are exploring its anti-tumor activities in different indications in additional clinical trials."

Dr. Qiu also indicated "It is a major step that Linperlisib has been accepted by the NMPA for the NDA application, and we are very optimistic about the outcome."

About Linperlisib

Linperlisib (YY-20394) is a highly selective and potent PI3Kδ inhibitor that has shown a favorable safety profile, exciting anti-tumor activities, and good PK and pharmaceutical properties as an oral once-a-day agent in late-stage clinical development. A phase 1 clinical trial was completed in 2020 demonstrating linperlisib to be a safe and tolerable agent, and a recommended phase 2 dose of 80 mg QD was established. Linperlisib was awarded NMPA Breakthrough Therapy status in China, leading to the current trial. In addition, linperlisib received FDA Orphan Drug Designations for FL, CLL/SLL, and T cell lymphoma. A clinical trial in r/r FL is launching in the US. Multiple linperlisib clinical trials being conducted in other lymphomas, solid tumors, and in combination with gemcitabine/oxaliplatin in r/r DLBCL. Preliminary results from a PTCL Phase1b study were reported at ASCO (Free ASCO Whitepaper) 2021, indicating an overall response rate of 70% with 33% CRs in 30 evaluable patients with r/r PTCL, a difficult to treat and aggressive form of lymphoma.

Ryvu Therapeutics Presents Positive Phase I Data for RVU120 at the Virtual 26th Annual Congress of the European Hematology Association. Phase I/II Data for SEL24 (MEN1703) presented by development partner Menarini

On June 11, 2021 Ryvu Therapeutics (WSE:RVU) reported the online publication of two posters and an oral presentation demonstrating clinical and pre-clinical activity of its selective CDK8/19 inhibitor RVU120 (previously SEL120) and the dual PIM/FLT3 inhibitor SEL24 (MEN1703), in-licensed by Menarini Group from Ryvu Therapeutics, at the Annual European Hematology Association (EHA) (Free EHA Whitepaper) 2021 Virtual Congress (Press release, Ryvu Therapeutics, JUN 11, 2021, View Source [SID1234583913])Annual European Hematology Association (EHA) (Free EHA Whitepaper) 2021 Virtual Congress.

RVU120: orally available CDK8/19 inhibitor

RVU120 (SEL120) is a highly selective first-in-class CDK8/CDK19 inhibitor, which has demonstrated efficacy in a number of solid tumor types in in vitro and in vivo models as well as in onco-hematological malignancies. The first-in-human (FIH) Phase I study with RVU120, in relapsed or refractory acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (HRMDS), is being conducted at 5 investigational sites in the US (View Source).

The data presented at EHA (Free EHA Whitepaper) 2021 covers the first four dose cohorts, in which RVU120 demonstrated favorable safety and PK profile. No DLTs were observed, and all of the reported SAEs were assessed as unlikely or not related to study drug.

Results are reported on the first five patients to receive treatment with RVU120, and the clinically relevant responses were observed in patients in the two highest dose cohorts reported:

The Cohort 3 (50mg dose, subsequently escalated to 75 mg) patient, with HRMDS, demonstrated an erythroid response from Cycle 5 to Cycle 8 and continues on RVU120 treatment in Cycle 13 with stable disease. An erythroid response reflects a reduction in red blood cell transfusions vs. baseline.
The Cohort 4 (75mg dose) patient, with relapsed/refractory AML, showed a response from C2 with persistence of skin leukemia, which completely resolved at C7 resulting in a CR. This patient was previously refractory to venetoclax + HMA, which is a patient population associated with poor prognosis.
Furthermore, translational data will be presented as part of an Oral Session and provide a potential linkage between in vitro data showing erythroid differentiation and erythroid response in the clinic. In vitro data demonstrate that RVU120 can induce erythroid cells to differentiate and therefore rescue anemia in preclinical models.

Presented results indicate strong erythroid differentiation potential of RVU120 (SEL120) in (Lin-) CD34+, that acquired genetic abnormalities resulting in arrested erythroid commitment, a characteristic of many MDS and AML subtypes. Detailed transcriptomic profiling strongly associated differentiation with enrichment of genes representing regulators of erythroid commitment and hemoglobin metabolism. Further studies are warranted to investigate efficacy of RVU120 (SEL120) in anemias associated with bone marrow failures in AML and MDS patients.

"We are excited to see early signs of clinical efficacy for RVU120 in both AML and high risk MDS patients who were previously treated with multiple lines of therapy. These patients had poor prognosis prior to treatment with RVU120, so we anticipate that RVU120 could serve an area of high unmet medical need. The translation of erythroid differentiation in vitro to potential erythroid responses in patients is an exciting clinical benefit as these patients require fewer red blood cell transfusions" – said Setareh Shamsili, MD, PhD, Chief Medical Officer and EVP at Ryvu Therapeutics.

Oral Presentation: "RVU120/SEL120 CDK8/19 inhibitor – a drug candidate for the treatment of MDS can induce erythroid differentiation in transformed CD34+ hematopoietic progenitor cells" (S164)

Presentation ID: p412-5
Date and Time: on-demand video recording is now available, followed by a Live Q&A Session on Wednesday, June 16 (13:00 – 13:45 CEST)
Poster Presentation: "CLI120-001 Phase1b Study of SEL120/RVU120 in patients with AML or High Risk MDS: Preliminary clinical and PK results from initial dose escalation cohorts" (EP480)

Poster ID: EP480
SEL24/MEN1703: orally available dual PIM/FLT3 inhibitor

A clinical poster on the first-in-human study of SEL24/MEN1703, the DIAMOND-01 trial conducted by Ryvu’s partner Menarini Group, reports four objective responses across the dose escalation (n=25) and cohort expansion (n=23) in patients with AML, with 3 of those 4 responders harboring an IDH mutation. Notably, three out of five patients with IDH mutations treated at doses of 75-125 mg achieved a CR/CRi, including a patient that relapsed on the IDH-inhibitor enasidenib. Furthermore, one patient with an IDH1 mutation achieved a CRi and underwent allogeneic-HSCT.

At the recommended dose (n=30) of 125mg/day as selected in the dose escalation phase, SEL24/MEN1703 showed a manageable safety profile. Most Grade 3 or higher treatment-emergent adverse events (TEAEs) were hematologic or infectious in nature.

"We are thrilled to share encouraging results for SEL24 (MEN1703) in treating patients with Acute Myeloid Leukemia," said Dirk Laurent, M.D., Global Therapeutic Area Head – Oncology at Menarini Ricerche, the R&D division of the Menarini Group. "The data, which is presented in our posters at both ASCO (Free ASCO Whitepaper) and EHA (Free EHA Whitepaper) annual meetings, provides a strong rationale for further clinical development, including the potential to focus on a molecularly defined subset of patients – AML patients with IDH mutations. This accomplishment reflects our sustained commitment to improving the lives of patients with difficult-to-treat cancer and underscores the value of our precision oncology approach."

Poster Presentation: "Results from DIAMOND-01 (CLI24-001) TRIAL: First in Human Study of SEL24/MEN1703, a Dual PIM/FLT3 Kinase Inhibitor, in Patients with Acute Myeloid Leukemia" (EP455)

Poster ID: EP455
All presentations and posters are now available online and can be obtained from conference site: View Source View Source

On June 11, at 1:00 PM CEST (7:00 AM ET), Ryvu Therapeutics will hold a conference call to discuss the data presented at EHA (Free EHA Whitepaper) 2021. Join the call at: live.ryvu.com
(or View Source)

About RVU120 (SEL120)

RVU120 (SEL120) is a selective first-in-class CDK8/CDK19 inhibitor, which has demonstrated efficacy in a number of solid tumor types in in vitro and in vivo models as well as in onco-hematological malignancies. The first-in-human (FIH) phase I study with RVU120, in relapsed or refractory AML or high-risk myelodysplastic syndromes (HRMDS), is currently enrolling patients at 5 investigational sites in USA (View Source).

Translational data suggest that RVU120 is particularly effective in undifferentiated AML STAT5-positive cancers. Administration of RVU120 in orthotopic AML patient derived xenograft models reduced tumor burden to the level undetectable in the peripheral blood, decreased splenomegaly and resulted in partial bone marrow recovery at well tolerated doses.

In addition, RVU120 has demonstrated single agent efficacy in multiple solid tumor models. On May 28, 2021, Ryvu’s Clinical Trial Application (CTA) to commence a single-agent, open-label Phase I/II trial, investigating the safety and efficacy of RVU120 (SEL120) in patients with relapsed/refractory metastatic or advanced solid tumors, was approved by the Polish Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, and the respective Central Ethics Committee.

On March 25, 2020, the U.S. Food and Drug Administration (FDA) granted an orphan drug designation (ODD) to RVU120, for the treatment of patients with acute myeloid leukemia (AML).

On April 7, 2021, U.S. Food and Drug Administration, FDA, placed a partial clinical hold on the first in human Phase Ib, dose escalation clinical trial of RVU120 in patients with relapsed/refractory (R/R) AML and high-risk MDS. Patients who are currently taking RVU120 may continue treatment. Ryvu continues to work closely with the FDA to resolve the partial clinical hold with the objective of resuming enrollment in the study.

RVU120 (SEL120) has been internally discovered by Ryvu and has received support from the Leukemia & Lymphoma Society Therapy Acceleration Program (TAP), a strategic initiative to partner directly with innovative biotechnology companies and leading research institutions to accelerate the development of promising new therapies for blood cancers.

About SEL24 (MEN1703)

SEL24 (MEN1703), a first-in-class, orally available, dual PIM/FLT3 kinase inhibitor discovered and initially developed by Ryvu Therapeutics and licensed to the Menarini Group. SEL24 (MEN1703) is currently evaluated in DIAMOND-01 trial (CLI24-001; clinicaltrials.gov identifier NCT03008187), a First-in-Human, Phase I/II, dose escalation and cohort expansion trial, as single agent for the treatment of patients with Acute Myeloid Leukemia (AML).

In the dose escalation part of DIAMOND-01 trial, SEL24 (MEN1703) demonstrated a manageable safety profile up to the recommended dose (RD) of 125 mg/day, along with initial evidence of anti-leukemic activity in a single agent setting, particularly in patients with IDH mutant disease either naïve or previously exposed to IDH inhibitors, warranting further investigation of the compound in molecularly defined subset of patients.

CEL-SCI Announces the Closing of $31.7 Million Bought Deal Offering

On June 11, 2021 CEL-SCI Corporation (NYSE American: CVM), a Phase 3 cancer immunotherapy company, reported the closing of the offering of 1,400,000 shares of its common stock at a price of $22.62 per share, for total gross proceeds of approximately $31.7 million, before deducting underwriting discounts and other offering expenses payable by the Company (Press release, Cel-Sci, JUN 11, 2021, View Source [SID1234583912]). Additionally, the Company has granted the underwriter a 30-day option to purchase up to 210,000 additional shares to cover over-allotments.

Kingswood Capital Markets, division of Benchmark Investments, LLC acted as sole book-running manager for the offering.

The shares of common stock described above were offered by CEL-SCI pursuant to a "shelf" registration statement on Form S-3 (File No. 333-226558) filed with the Securities and Exchange Commission (SEC) and the accompanying prospectus contained therein. The offering of the shares of common stock were made only by means of a prospectus, including a prospectus supplement, forming a part of the effective registration statement. A preliminary prospectus supplement and the accompanying prospectus relating to and describing the terms of the offering was filed with the SEC. A final prospectus supplement was also filed with the SEC. Copies of the preliminary prospectus supplement, final prospectus supplement and the accompanying prospectus relating to this offering may be obtained on the SEC’s website at View Source or by contacting Kingswood Capital Markets, Attention: Syndicate Desk, 590 Madison Avenue, 39th Floor, New York, NY 10022, by email at [email protected], or by telephone at (212) 404-7002.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy any of the securities described herein, 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.