On July 21, 2021 Ascentage Pharma (6855.HK), a globally focused biotechnology company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported that the US Food and Drug Administration (FDA) recently granted an Orphan Drug Designation (ODD) to the company’s MDM2-p53 inhibitor, APG-115 (alrizomadlin), for the treatment of stage IIB-IV melanoma (Press release, Ascentage Pharma, JUL 21, 2021, View Source [SID1234585042]). This marks the fifth ODD granted to alrizomadlin, after those for the treatment of gastric cancer, acute myeloid leukemia, soft tissue sarcoma, and retinoblastoma. To date, Ascentage Pharma has obtained a total of twelve ODDs from the FDA, continuing to set the record for the number of ODDs granted to any Chinese biopharmaceutical company.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The term "orphan drugs" refers to pharmaceutical products developed for the prevention, diagnosis, and treatment of rare diseases or conditions. In the United States, an orphan indication is defined as a disease or condition with a prevalence of less than 200,000 patients in the country. Since the Orphan Drug Act was passed in 1983, the US government has provided incentives and policy support to encourage development of orphan drugs. This ODD by the FDA qualifies alrizomadlin for a range of development incentives, including a tax credit on expenditures incurred in clinical studies, a waiver of the New Drug Application (NDA) fee, possible research grant awarded by the FDA, and most importantly, 7 years of US market exclusivity upon approval.

Melanoma is a potentially deadly dermatologic malignancy that has been increasingly prevalent globally. The current lifetime risk of developing melanoma is 1 in 63 in the US1. In 2019, an estimated 96,480 patients have been diagnosed with melanoma and about 7230 patients with melanoma have died in the United States2. The prognosis of patients with of melanoma is closely associated with the stage of the disease at diagnosis. A US Surveillance, Epidemiology, and End Results (SEER) database review of melanoma cases from 2011 to 2015 identified approximately 75% of patients were diagnosed at stage I, 15% at stage II, 7.5% at stage III, and 2.5% at stage IV3.

Since 2011, remarkable progress has been achieved in the clinical treatment of patients with metastatic or unresectable melanoma. Targeted therapies such as mitogen-activated protein (MAP) kinase inhibitors and immunotherapies have dramatically improved patients’ overall survival and quality of life4-6. Immunotherapies, namely immune checkpoint inhibitors (ICIs) such as anti-CTLA-4, anti-PD-1, and anti-PD-L1 monoclonal antibodies have been extensively studied and broadly used in clinical treatment. However, significant number of patients will eventually develop resistance to ICIs, and there is no approved treatment yet for patients with ICI-resistant melanoma.

Being developed by Ascentage Pharma, alrizomadlin is an orally administered, selective, small-molecule MDM2-p53 inhibitor. Preclinical studies showed that alrizomadlin combined with PD-1 blockade enhances antitumor activities by triggering adaptive antitumor immunity. At the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, Ascentage Pharma reported updated results from a Phase II study of alrizomadlin in combination with pembrolizumab that demonstrated promising antitumor activity and safety. The PD-1/PD-L1 inhibitor-resistant melanoma cohort which was treated with alrizomadlin plus pembrolizumab reported 1 patient with complete response, an objective response rate (ORR) of 24.1%, and a disease control rate of 55.2%. These results signified the synergy between alrizomadlin and immune-oncologic drugs, and a potential regimen that could bring hope to patients with ICI-resistant melanoma.

"At present, there is a large unmet medical need for the treatment of melanoma. Therefore, this ODD for alrizomadlin bears tremendous significance," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "As the fifth ODD granted to alrizomadlin, and the twelfth obtained by Ascentage Pharma, this designation reaffirms Ascentage Pharma’s leadership in the number of ODDs granted to any Chinese biopharmaceutical company, demonstrating our capabilities in global innovation. Moving forward, we will continue to pursue our mission of addressing unmet medical needs in China and around the world. The FDA’s supporting policy for orphan drug development will help us to further accelerate the clinical development of alrizomadlin and other drug candidates in our pipeline and hopefully we can bring these potential novel therapies to patients as soon as possible."

On July 21, 2021 Ensysce Biosciences, Inc. ("Ensysce" or the "Company") (NASDAQ: ENSC, OTC: ENSCW), a clinical stage biotech company with proprietary technology platforms to reduce the economic and social burden of prescription drug abuse and overdose, reported that it will host a virtual investor day on Tuesday, July 27, 2021 from 11:00 am to 12:00 pm EDT (Press release, Ensysce Biosciences, JUL 21, 2021, View Source [SID1234585504]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Ensysce CEO Dr. Lynn Kirkpatrick and CFO Dave Humphrey will present alongside other members of the Company’s executive management team. There will be a 30-minute question and answer session following the Company’s presentation.

Registration for the event can be found here. Interested parties may submit questions in advance of the event by emailing [email protected]. A recording of the event as well as the accompanying presentation will be provided on the Company’s website following the conclusion of the event.

On July 21, 2021 Celyad Oncology SA (Euronext & Nasdaq: CYAD) (Brussels:CYAD) (Paris:CYAD) (NASDAQ:CYAD) (Celyad Oncology or the Company), a clinical-stage biotechnology company focused on the discovery and development of chimeric antigen receptor T cell (CAR T) therapies for cancer, reported a new preclinical allogeneic armored CAR T candidate developed from its shRNA platform and data updates to the shRNA-based allogeneic candidate CYAD-211 for r/r MM and allogeneic candidate CYAD-101 for mCRC today during a research and development day hosted by the Company’s management team (Press release, Celyad, JUL 21, 2021, View Source [SID1234585009]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are ushering in a new era of allogeneic CAR T candidates using novel technological advances, including our proprietary shRNA platform for allogeneic CAR T production and now the addition of our ‘armored’ CAR capabilities with co-expression of the cytokine IL-18," said Filippo Petti, Chief Executive Officer of Celyad Oncology. "We believe the advances we’re making may address many of the current modality limitations and have the potential to provide real-world benefits for patients, including more accessible CAR T cell treatment options, if approved. This continued technological innovation, which is currently being validated in ongoing clinical studies, establishes Celyad Oncology as a leader in this adoptive cell therapy space."

Latest Program Updates

CYAD-211 – Allogeneic shRNA-based, anti-BCMA CAR T for r/r MM

CYAD-211 is the Company’s first shRNA-based allogeneic CAR T candidate, which co-expresses a BCMA targeting chimeric antigen receptor while using shRNA to knockdown expression of the CD3ζ component of theT-cell receptor (TCR)
Currently, CYAD-211 is being evaluated in the Phase 1 IMMUNICY-1 trial in r/r MM following preconditioning with cyclophosphamide (300 mg/m²) and fludarabine (30 mg/m²) given three consecutive days.
In June, preliminary data from the Phase 1 IMMUNICY-1 trial was presented at the European Hematology Association (EHA) (Free EHA Whitepaper) congress demonstrating no dose limiting toxicity (DLT), Graft-versus-Host disease (GvHD) or CAR T-cell-related encephalopathy syndrome (CRES) in the first two dose levels (30×106 and 100×106 cells per infusion) of the trial. Two of the five evaluable patients at the first two dose levels achieved a partial response. In addition, CYAD-211 cells were detected by PCR-based methods in all six patients with evidence of a dose dependent increase in cell engraftment.
Recent data from the first patient at dose level three (300×106 cells per infusion) continues to show dose dependent engraftment with no GvHD reported to date.
Enrollment in the trial is ongoing with plans to explore higher doses of preconditioning regimens in future cohorts.
CYAD-203 – Allogeneic shRNA-based, IL-18-armored NKG2D CAR T for Solid Tumors

CYAD-203 is the Company’s first armored CAR T candidate engineered to co-express the cytokine interleukin-18 (IL-18) with the NKG2D CAR receptor. To the Company’s knowledge, this therapy is on track to be first ever IL-18 secreting allogeneic CAR T candidate.
IL-18 is a proinflammatory cytokine that directly potentiates the anti-cancer activity of CAR T cells while also altering the balance of pro- and anti-inflammatory cells within tumor tissue.
Investigational New Drug (IND)-enabling studies are currently ongoing. Submission of the IND application for CYAD-203 for treatment of solid tumors is expected in mid-2022.
CYAD-101 – Allogeneic TIM-based NKG2D CAR T for mCRC

To the Company’s knowledge, CYAD-101 is the first investigational allogeneic CAR T candidate to generate evidence of clinical activity for the treatment of a solid tumor indication. This is based on data from the dose-escalation segment of the alloSHRINK Phase 1 trial evaluating CYAD-101 following FOLFOX (combination of 5-fluorouracil, leucovorin and oxaliplatin) preconditioning chemotherapy for the treatment of advanced metastatic colorectal cancer (mCRC).
Initial data from the dose expansion cohort evaluating CYAD-101 (1×109 cells per infusion) following FOLFIRI (combination of 5-fluorouracil, leucovorin and irinotecan) preconditioning chemotherapy showed CYAD-101 was generally well-tolerated with no dose limiting toxicities or evidence of GvHD. Overall, nine out of ten evaluable mCRC patients showed stable disease at first tumor assessment.
Data also showed shorter persistence of CYAD-101 cells observed after FOLFIRI preconditioning as compared to FOLFOX preconditioning. Based on better CYAD-101 cell kinetics and clinical activity data from the alloSHRINK FOLFOX cohort, the Company submitted a protocol amendment to regulatory agencies to modify the Phase 1b KEYNOTE-B79 trial to incorporate FOLFOX as preconditioning chemotherapy.
The KEYNOTE-B79 trial to evaluate CYAD-101 with Merck’s anti-PD­1 therapy, KEYTRUDA (pembrolizumab), in refractory mCRC patients with microsatellite stable / mismatch-repair proficient disease is expected to be initiated during the fourth quarter of 2021.
Business Update

Celyad Oncology has acquired an exclusive license from the Moffitt Cancer Center for an antibody directed to Tumor-associated glycoprotein (TAG-72), which will form the basis of a T cell engager to be used with our proprietary shRNA platform technology. TAG-72 has been shown to be expressed in a wide variety of epithelial malignant tissues including breast, colon and pancreatic cells and will expand the Company’s program portfolio in solid tumor targets.
Upcoming Milestones

Additional clinical activity data for the Phase 1 IMMUNICY-1 trial of CYAD-211 for r/r MM are expected during second half 2021.
Study initiation for KEYNOTE-B79 Phase 1b is expected early fourth quarter 2021.
Submission of an IND application for CYAD-203 is expected in mid-2022.
Report additional data from the dose-escalation Phase 1 CYCLE-1 trial evaluating CYAD-02 in relapsed/refractory acute myeloid leukemia and myelodysplastic syndrome in mid-2021.

On July 21, 2021 Vedanta Biosciences, Inc., a leading clinical-stage microbiome company developing a new category of oral therapies using defined bacterial consortia manufactured from clonal cell banks, reported the closing of a $68 million Series D financing and provided a pipeline update (Press release, Vedanta Biosciences, JUL 21, 2021, View Source [SID1234585025]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The Series D financing was led by affiliates of Magnetar Capital. Other participants in the financing were new and existing investors including Verition Fund Management, Fosun Health Capital, co-founder PureTech Health, Rock Springs Capital, Skyviews Life Science, JSR Corporation, SymBiosis LLC, Shumway Capital, Health for Life Capital (Seventure Partners), and other institutional investors. The round also includes a $25 million investment from Pfizer as part of the Pfizer Breakthrough Growth Initiative, which was announced in January 2021.

Vedanta plans to use the proceeds to advance its pipeline of defined bacterial consortia, including progressing VE303 into a Phase 3 clinical trial in patients at high risk for recurrent CDI, initiating a Phase 2 clinical trial of VE202 in mild to moderate ulcerative colitis, and continuing to advance programs in additional indications.

"We are delighted to welcome the new investors in our Series D round and are grateful to our existing shareholders and partners for their continued support," said Bernat Olle, Ph.D., Co-founder and Chief Executive Officer of Vedanta Biosciences. "Since our last funding round, we have made significant progress advancing defined bacterial consortia as a new modality for infectious and immune-mediated diseases. This most recent financing, together with the support we receive from BARDA for our CDI program, will enable us to advance mid- and late-stage programs in CDI and IBD, as well as support early exploratory clinical studies in additional indications."

"Drugs based on defined bacterial consortia are a promising new therapeutic modality with the potential to transform medicine, and Vedanta is the leader in this category, with a state-of-the-art discovery platform, field-leading GMP manufacturing capabilities, and an advanced pipeline," said Ted Koutouzis, MD, Managing Director of Fiscus Venture and Reimagined Ventures, affiliates of Magnetar. "We are proud to support the company’s efforts."

Vedanta’s Pipeline

Vedanta Biosciences is developing a potential new category of oral therapies based on rationally defined consortia of bacteria derived from the human microbiome. All of the Company’s pipeline programs are wholly owned.

Company-Sponsored Programs

VE303 for the Prevention of Recurrence in High-risk Patients with Clostridioides difficile (CDI) Infection

VE303 consists of 8 clonal human commensal bacterial strains selected for their ability to provide colonization resistance to C. difficile.
In a Phase 1 healthy-volunteer study, VE303 showed rapid, durable, and dose-dependent colonization and accelerated gut microbiota restoration after a course of antibiotics.
Vedanta is currently evaluating VE303 in a Phase 2 clinical trial in patients at high risk of recurrent CDI and will report results from this trial in Q3 2021.
In 2020, Vedanta was awarded up to $76.9 million of federal funds from the Department of Health and Human Services; Office of the Assistant Secretary for Preparedness and Response; Biomedical Advanced Research and Development Authority, under Contract No. 75A50120C00177, to partially fund the development of VE303. This was the first-ever grant from BARDA in the microbiome field.
The Company expects to complete the build-out of its Phase 3 and commercial launch cGMP manufacturing facility for supply of VE303 by the end of 2021.
The company plans to initiate a Phase 3 trial in mid-2022.
VE202 for the Treatment of Inflammatory Bowel Disease (IBD)

VE202 consists of 16 clonal human commensal bacterial strains selected for their ability to induce regulatory T cells in the gut mucosa, decolonize pro-inflammatory organisms, and strengthen the epithelial barrier.
In June 2021, Vedanta presented positive Phase 1 topline data of VE202 in healthy volunteers at the International Human Microbiome Consortium Congress. VE202 was generally safe and well tolerated at all doses and demonstrated durable and dose-dependent colonization.
Vedanta plans to initiate a Phase 2 clinical trial of VE202 in patients with mild to moderate ulcerative colitis in the second half of 2021.
VE202 is being developed in part through funding provided by the Pfizer Breakthrough Growth Initiative.
VE800 for the Treatment of Advanced and Metastatic Tumors

VE800 consists of 11 clonal human commensal bacterial strains selected for their ability to induce CD8+ T cells, potentiate anti-tumor activity, and enhance the effects of checkpoint inhibitors.
The Company is nearing completion of Stage 1 of an open-label Phase 1 study to evaluate the safety and initial clinical activity of VE800 in combination with Bristol Myers Squibb’s Opdivo (nivolumab) in 54 patients across select types of advanced or metastatic cancers.
This trial is being done under a collaboration and supply agreement with Bristol Myers Squibb.
To date, VE800 has demonstrated an acceptable safety and tolerability profile, though the observed response rates did not meet the prespecified criteria to expand into the next stage of the study. Vedanta is analyzing blood, stool, and tumor samples from patients in whom response or disease control was observed, to profile patient subtypes that might benefit from microbiome manipulation. The company plans to present the results at a future medical conference.
The Company will continue work to identify cancer settings and patient populations that might benefit from microbiome manipulation with its defined bacterial consortia.
Preclinical Programs

VE707 is a preclinical program for the prevention of infection by several problematic Gram-negative Enterobacteriaceae, which are some of the most common hospital-acquired pathogens. Vedanta has received funding from Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) of up to $7.4 million, plus up to $3.5 million more if certain milestones are met, to advance VE707. The company expects to select a development candidate in H2 2021.
Investigator-Sponsored Studies

VE416 in Peanut Allergy

VE416 consists of 7 bacterial strains of the Clostridia class, which were selected based on the ability to induce immune tolerance in the gut.
A Phase 1/2, investigator-sponsored clinical study is underway at Massachusetts General Hospital, exploring use of VE416 both as a monotherapy and in combination with an oral peanut immunotherapy over the course of several months.
Topline data from the Phase 1/2 clinical trial is expected to be reported in 2022, subject to investigator timelines.
VE303 in Hepatic Encephalopathy

A new Phase 2 investigator-sponsored trial evaluating VE303 in patients with hepatic encephalopathy (HE) was recently initiated by the University of Michigan Hospitals-Michigan Medicine. The randomized, double-blind, placebo-controlled trial is planned to enroll up to 18 adult patients with a confirmed diagnosis of cirrhosis and history of at least one episode of overt HE.
FJS Consultants Limited acted as a placement agent for Vedanta’s investors in China. BARDA is the Biomedical Advanced Research and Development Authority, part of the Office of the Assistant Secretary for Preparedness and Response at the U.S. Department of Health and Human Services.

On July 21, 2021 Alloy Therapeutics and Echo Investment Capital reported the formation of Wheeler Bio, a new biomanufacturing company built to accelerate the translation of therapeutic innovation into clinical impact (Press release, Alloy Therapeutics, JUL 21, 2021, View Source [SID1234585043]). Wheeler’s comprehensive discovery-to-IND programs are designed to provide emerging biopharma companies a faster and more predictable path to the clinic.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

With an initial focus on antibody therapeutics, Wheeler’s biomanufacturing programs will seamlessly integrate with Alloy Therapeutic’s preclinical antibody platforms and discovery capabilities. Wheeler’s state-of-the-art development and cGMP operations and business headquarters are located in Oklahoma City, OK and are supported by a pilot lab inside Alloy’s Boston, MA facility.

"Accelerating the translation of therapeutic innovation into clinical impact in the biopharma industry requires new kinds of biomanufacturing businesses. We created Wheeler Bio to provide best-in-class biomanufacturing speed, capabilities, and service to the next generation of drug developers," stated Dr. Jesse McCool, co-founder and CEO of Wheeler. "Through our parallel integration with discovery and unique partnering model, we will be able to offer customers groundbreaking turnaround times at fair prices."

"Finding a CDMO that cares as much about your preclinical batches as your commercial batches is a challenge we regularly face in drug development. Alloy is excited to partner with Wheeler and is confident that Jesse and his team will deliver the turnkey and high-quality CMC services that Alloy’s ecosystem of partners require to achieve their clinical goals," said Errik Anderson, Founder and CEO of Alloy Therapeutics. "What Wheeler is building aligns completely with Alloy’s mission to democratize access to foundational drug development technologies and capabilities."

Wheeler launched its Boston-based operations in Q1 2021 and will open its 35,000 sq. ft. cGMP Oklahoma City facility in Q4 2022. Through its partnership with Echo Investment Capital, Wheeler will have preferred access to expand its biomanufacturing offering to commercial scale production in the recently announced 400,000 sq. ft. manufacturing complex in the Oklahoma City Innovation District led by commercial real estate developers Richard Tanenbaum and Mark Beffort.

"Oklahoma City’s investment in bioscience and workforce development over the last 30 years has allowed Echo to rapidly enter the biomanufacturing arena with a compelling offering that connects coastal biopharmaceutical companies to critical resources at industry leading customer-first terms," said Christian Kanady, Founding Partner of Echo Investment Capital. "Our close affiliation with the OKC Innovation District and the greater healthcare ecosystem allows us to connect Wheeler’s customers with exceptional development and clinical resources like Wheeler, Stephenson Cancer Center, Harold Hamm Diabetes Center, and Oklahoma Children’s Hospital."