On September 8, 2020 BeyondSpring Inc. (the "Company" or "BeyondSpring") (NASDAQ: BYSI), a global biopharmaceutical company focused on developing innovative immuno-oncology cancer therapies to transform the lives of patients with unmet medical needs, reported that its lead asset, first-in-class agent Plinabulin, has received the Breakthrough Therapy Designation (BTD) for the chemotherapy-induced neutropenia (CIN) indication from both the U.S. Food and Drug Administration (FDA) and China’s Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) (Press release, BeyondSpring Pharmaceuticals, SEP 8, 2020, View Source [SID1234585747]).

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The FDA’s BTD is intended to expedite the development and review of a drug candidate that is planned to treat a serious or life-threatening disease or condition in which clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints. The CDE in China established its BTD program in July 2020 to facilitate the research and development of innovative drugs that treat severe life-threatening or quality-of-life impairing diseases with no existing therapy or with proven evidence to demonstrate clear clinical benefits compared to existing therapies. Products with BTD from the CDE may be considered for conditional approval and priority review when submitting New Drug Applications (NDAs).

"Receipt of Breakthrough Therapy Designation from the FDA acknowledges both the significant unmet need among patients with CIN and the highly encouraging clinical results generated by Plinabulin," said Douglas Blayney, M.D., global Principal Investigator for Plinabulin’s CIN studies and Professor of Medicine at the Stanford University School of Medicine. "This should expedite Plinabulin’s move into the clinic, which is beneficial for patients. The currently approved CIN prevention agents are all G-CSF-based and not available to all patients. Even with the use of G-CSFs, over 80 percent of cancer patients undergoing chemotherapy may still experience Grade 4 neutropenia, which could lead to severe infection, hospitalization and even death. Thus, CIN still represents an unmet medical need."

"The clinical profile Plinabulin has shown truly represents a breakthrough in the CIN space since G-CSFs," added Ramon Mohanlal, M.D., Ph.D., MBA, Chief Medical Officer and Executive Vice President, Research and Development, at BeyondSpring. "We look forward to continuing to work with the FDA as we advance the development of Plinabulin to address this urgent medical need."

The Breakthrough Therapy application is based on the strength of the totality of the clinical data generated so far:

Positive interim analysis results from the PROTECTIVE-2 Phase 3 study – The clinically meaningful primary endpoint was the prevention of severe neutropenia, an "industry first," building on the previous standard for approval, the Duration of Severe Neutropenia (DSN). In the protocol-specified interim analysis, Plinabulin, in combination with Neulasta, was significantly better than Neulasta alone in achieving the primary endpoint with p<0.01, along with a well-tolerated safety profile and fewer Grade 4 adverse events, compared to Neulasta alone.
These results were further strengthened by the Company’s other CIN studies that have confirmed Plinabulin’s early onset action in Week 1 with protecting neutrophils in various cancer types and various chemotherapies, which is complementary to Week 2 neutrophil protection with G-CSFs.
The Company expects to report the full PROTECTIVE-2 Phase 3 topline data in Q4 2020 and file an NDA with the FDA by the end of 2020. The Company has submitted an NDA for Plinabulin for the CIN indication to the NMPA on a rolling basis in Q1 2020.

About Chemotherapy-Induced Neutropenia (CIN)
CIN is a common side effect in cancer patients undergoing treatment that involves the destruction of a type of white blood cell, the neutrophil, which is a patient’s first line of defense against infections. Patients with Grade 4 (severe) neutropenia have an abnormally low concentration of neutrophils, which may lead to infections, hospitalization and death.

G-CSFs are the current standard of care for CIN prevention. However, G-CSFs have limitations in reducing Grade 4 neutropenia with high-risk chemotherapy. Neutropenia, if severe enough, may cause doctors to lower target doses of chemotherapy, end therapy early and / or delay chemotherapy cycles, each of which has a negative effect on long-term outcomes of cancer care.

Despite these limitations annual global use of G-CSFs is more than 4.3 million cycles per year (CPY). The U.S. (1.3 million CPY) and China (1.6 million CPY) account for more than two-thirds of the global CIN market. Plinabulin’s demonstrated clinical profile in combination with G-CSFs has the potential to build on this existing base and improve the standard of care for patients and practitioners.

About Plinabulin
Plinabulin, BeyondSpring’s lead asset, is a differentiated immune and stem cell modulator. Plinabulin is currently in late-stage clinical development to increase overall survival in cancer patients, as well as to alleviate chemotherapy-induced neutropenia (CIN). The durable anticancer benefits of Plinabulin have been associated with its effect as a potent antigen-presenting cell (APC) inducer (through dendritic cell maturation) and T-cell activation (Chem and Cell Reports, 2019). Plinabulin’s CIN data highlights the ability to boost the number of hematopoietic stem / progenitor cells (HSPCs), or lineage-/cKit+/Sca1+ (LSK) cells in mice. Effects on HSPCs could explain the ability of Plinabulin to not only treat CIN but also to reduce chemotherapy-induced thrombocytopenia and increase circulating CD34+ cells in patients.

About Plinabulin in CIN Study
The PROTECTIVE-1 (Study 105) and PROTECTIVE-2 (Study 106) trials are both multicenter, double-blind, active controlled Phase 3 trials to support Plinabulin’s broad application in preventing CIN: Plinabulin for concurrent administration with myelosuppressive chemotherapy regimens in patients with non-myeloid malignancies for the presentation of chemotherapy-induced neutropenia (CIN).

PROTECTIVE-1 (Study 105)
This study was designed to evaluate the safety and efficacy in non-small cell lung cancer (NSCLC), breast cancer and prostate cancer patients with risk factors, treated with docetaxel (Day 1 dose) in a 21-day cycle with a single dose of Plinabulin (40mg, Day 1 dose) versus a single dose of Neulasta (6mg, Day 2). Docetaxel is one example of an intermediate-risk chemotherapy. This is a non-inferiority study in CIN efficacy comparing Plinabulin and Neulasta in high-risk patients (intermediate chemotherapy, plus one or more additional risk factor). Study 105 Phase 3 interim data had achieved statistical significance based on the primary endpoint of the Duration of Severe Neutropenia (DSN) in the first cycle.

PROTECTIVE-2 (Study 106)
This study was designed to evaluate the safety and efficacy in breast cancer, treated with docetaxel, doxorubicin and cyclophosphamide (TAC, Day 1 dose) in a 21-day cycle with Plinabulin (40 mg, Day 1 dose) in combination with Neulasta (6 mg, Day 2 dose) versus a single dose of Neulasta (6 mg, Day 2 dose) alone. TAC is an example of high-risk chemotherapy. Plinabulin and G-CSFs have complementary mechanisms in preventing chemotherapy-induced neutropenia (CIN). This is a superiority study in CIN efficacy in the rate of Grade 4 neutropenia prevention (primary endpoint), comparing the combination head-to-head against Neulasta, and is currently enrolling. Literature shows that the Grade 4 neutropenia rate for TAC and Neulasta at 6 mg is 83 to 93 percent, which presents severe unmet medical needs.

Covance is the clinical contract research organization (CRO) for patient recruitment and monitoring of global sites for this study. The CIN studies are conducted in over 60 clinical centers in the U.S., China and Europe. In addition, Absolute Neutrophil Count (ANC) data, which is used to calculate these endpoints, was obtained through central laboratory assessments by Covance Bioanalytical Methods using standardized and validated analytical tests.

On September 8, 2020 Athenex, Inc. (Nasdaq: ATNX), a global biopharmaceutical company dedicated to the discovery, development and commercialization of novel therapies for the treatment of cancer, reported that it intends to offer and sell, subject to market conditions, 10,000,000 shares of its common stock in an underwritten public offering (Press release, Athenex, SEP 8, 2020, View Source [SID1234573873]). In addition, Athenex expects to grant the underwriters a 30-day option to purchase up to an additional 1,500,000 shares of common stock at the public offering price, less underwriting discounts and commissions. The offering is subject to market conditions, and there can be no assurance as to whether or when the offering may be completed, or as to the actual size or terms of the offering.

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SVB Leerink, RBC Capital Markets and Evercore ISI are acting as joint book-running managers and Oppenheimer & Co. is acting as lead manager for the offering.

The securities described above are being offered by Athenex pursuant to a shelf registration statement on Form S-3 (File No. 333-227492) that was filed with the Securities and Exchange Commission (the "SEC") on September 24, 2018 and became effective upon filing. A preliminary prospectus supplement relating to and describing the terms of the offering will be filed with the SEC and will be available on the SEC’s website at www.sec.gov. Copies of the preliminary prospectus supplement and the accompanying prospectus relating to this offering, when available, may be obtained from: SVB Leerink LLC, Attention: Syndicate Department, One Federal Street, 37th Floor, Boston, MA 02110, by telephone at 1-800-808-7525, ext. 6218, or by email at [email protected]; RBC Capital Markets, LLC, Attention: Equity Syndicate, 200 Vesey Street, 8th Floor, New York, NY 10281, by telephone at (877) 822-4089, or by email at [email protected]; and Evercore Group L.L.C., Attention: Equity Capital Markets, 55 East 52nd Street, 36th Floor, New York, New York 10055, or by telephone at (888) 474-0200, or by email at [email protected].

This press release shall not constitute an offer to sell or a solicitation of an offer to buy these securities, nor shall there by any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or jurisdiction.

On September 8, 2020 Manifold Bio, a spinout from George Church’s lab at Harvard Medical School focused on dramatically increasing the throughput of protein therapeutics testing in vivo, announced the close of a $5.4 million Series Seed investment round (Press release, Manifold Bio, SEP 8, 2020, View Source [SID1234572307]). Playground Global led the round and was joined by pre-seed lead Fifty Years and early investors GETTYLAB and Allston Venture Fund. The investment will enable the company to expand the team and accelerate the development of a proprietary protein quantitation platform.

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Manifold Bio was founded by CEO Gleb Kuznetsov, Ph.D., and CSO Pierce Ogden, Ph.D., along with George Church, Ph.D., Professor of Genetics at Harvard Medical School and the Wyss Institute for Biologically Inspired Engineering. They are joined by co-founder and Head of Business Development Shane Lofgren who previously helped build companies that emerged from Stanford and MD Anderson.

"The most valuable data on a candidate drug comes from testing it in a living system," says co-founder and CEO Gleb Kuznetsov. "Despite the advent of high-throughput technologies early in the discovery pipeline, drug development teams eventually run into the bottleneck of testing only one molecule at a time in the most relevant biological assays and animals. At Manifold Bio, we’re focused on building a platform that removes this barrier and allows us and our partners to pursue cures for devastating diseases much more rapidly."

"We’ve seen exponential advances that allow us to synthesize millions of strands of DNA and sequence billions of DNA bases, but the number of drugs that can be tested in relevant animal models remains in the single digits," said co-founder George Church, who introduced Manifold Bio in a keynote last week at PEGS, the premier industry protein engineering conference. "With the technology and talented interdisciplinary team we’re building at Manifold Bio, we’ll be able to bring the massively parallel economics of multiplexing to bear on engineering protein therapeutics."

Manifold Bio’s platform will allow multiplexed (pooled) tracking and quantification of thousands of unique protein designs, including monoclonal antibodies and other protein therapeutic scaffolds, across a range of complex testing environments.

"By turning protein engineering into a DNA synthesis and sequencing problem, we’re able to learn biological design principles directly from rich data generated by our novel in vivo assays," co-founder and CSO Pierce Ogden said. Last year, Ogden published a ground-breaking paper in Science demonstrating in vivo screening of more than 200,000 gene therapy virus designs. "Now, we’re building the platform technology for the larger space of protein therapeutics. The key is making it possible to test and quantify mixtures of designs directly where it matters–in vivo disease models. These advances will pave the way toward our goal of transforming drug discovery into measurement-driven drug design."

"Too many of the drug discovery startups we see are focused primarily on computation and improving the beginning of the drug development funnel, only to revert to traditional and painfully inefficient artisanal methods as therapies approach the clinic," said Jory Bell, Partner at Playground Global. "Manifold Bio has developed an entirely new approach to engineering which profoundly impacts all phases of development."

"By enabling high throughput in vivo screening of protein therapeutics, Manifold Bio can discover new biologics at scale," said Seth Bannon, Founding Partner at Fifty Years. "Their approach allows generating valuable data faster and at a lower financial and ethical cost, leading to cures that have evaded traditional methods."

Playground Global’s Jory Bell will join Manifold Bio’s board of directors.

On September 8, 2020 Silence Therapeutics plc, AIM:SLN and NASDAQ: SLN ("Silence" or "the Company") a leader in the discovery, development and delivery of novel short interfering ribonucleic acid (siRNA) therapeutics for the treatment of diseases with significant unmet medical need, reported that provides a research and development update (Press release, Silence Therapeutics, SEP 8, 2020, View Source [SID1234568596]).

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Pipeline progress

SLN360

·Silence’s wholly owned lead product candidate SLN360 for the treatment of cardiovascular disease associated with high Lipoprotein(a), or Lp(a), levels, has received approval from the Food and Drug Administration (FDA) for an Investigational New Drug (IND) application to start dose escalation studies in healthy volunteers and secondary prevention patients with elevated Lp(a). SLN360 is designed to address increased cardiovascular risk associated with raised levels of Lp(a), which is considered to affect up to 10% of the world’s population. Whilst we are aiming to start dosing healthy volunteers in the Phase 1 trial by the end of the year, the Covid-19 pandemic may put this timing at risk.

SLN124

Silence has initiated dosing in its randomised, double-blind, placebo-controlled Phase 1 single-ascending dose study of SLN124, the Company’s wholly owned product candidate for beta-thalassaemia and myelodysplastic syndrome (MDS), in up to 24 healthy volunteers. This marks the first dose of a Silence siRNA therapeutic delivered to humans using the Company’s proprietary GalNAc-siRNA platform. GalNAc is a naturally occurring sugar that binds specifically to a receptor which is highly expressed on liver cells, or hepatocytes. Coupling GalNAc sugars to stabilized siRNA molecules allows them to specifically target liver cells and carry out their function.
The FDA recently granted SLN124 orphan drug designation (ODD) for the treatment of adult beta-thalassemia. The FDA previously granted SLN124 ODD for MDS and rare paediatric designation for beta-thalassaemia. SLN124 also has ODD for the treatment of beta-thalassaemia from the European Medical Agency.
Complement Collaboration

·Silence is pleased to announce work commenced on the second target being explored under its complement pathway RNAi collaboration with Mallinckrodt, which triggered a $2.0 million research milestone payment to the Company. Silence would be entitled to receive an additional $2.0 million research milestone payment if work commences on a third target in the collaboration.

Iain Ross, Executive Chairman of Silence Therapeutics, said: "In what has been a busy and successful year for Silence, we have continued to make significant progress with our R&D pipeline. We are delighted to announce today that we have received FDA approval of the IND application for our wholly owned lead product candidate, SLN360, which is designed to address a significant unmet medical need in cardiovascular disease for people born with high Lp(a) levels. We have also made strong progress with our wholly owned product candidate, SLN124, having now dosed the first healthy volunteer. This marks the first dose of a Silence GalNAc-siRNA given to humans and is the culmination of several years’ work in developing this platform. This is truly an exciting time for Silence and we look forward to providing further updates as we move ahead."

On September 8, 2020 Genenta Science, a clinical-stage biotechnology company pioneering the development of a hematopoietic stem cell gene therapy for cancer (Temferon), reported that they will present data from the TEM-GBM study at the Advanced Therapies Congress & Expo 2020 (Press release, Genenta Science, SEP 8, 2020, View Source [SID1234568502]).

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Dr. Carlo Russo, Chief Medical Officer and Head of Development at Genenta, will provide an overview of Temferon, the company’s pipeline and the latest preliminary clinical data in patients affected with glioblastoma multiforme, on September 9, at 6.50pm CET.