On September 10, 2021 BeyondSpring Inc., a global biopharmaceutical company focused on the development of innovative cancer therapies, reported its financial results for the second quarter ended June 30, 2021 and provided an update on recent corporate events (Press release, BeyondSpring Pharmaceuticals, SEP 10, 2021, View Source;utm_medium=rss&utm_campaign=beyondspring-announces-second-quarter-2021-financial-results-and-provides-a-corporate-update [SID1234587508]).

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"We had a very productive first half of 2021. Importantly, we were thrilled to announce positive data from our registrational trial of plinabulin in 2nd/3rd line NSCLC, which showed significant improvement in overall survival, especially the doubling of 2-year and 3-year survival in the plinabulin and docetaxel arm vs. docetaxel alone. This underscores plinabulin’s immune durable anti-cancer benefit, which could be the gateway for its development in multiple cancer indication in triple IO combos. With the significant survival benefit and significant reduction in severe neutropenia of chemotherapy, we expect that plinabulin’s optimum profile for patient’s need is just beginning to be revealed. These data set the stage for multiple near-term catalysts over the next 6-12 months," said Dr. Lan Huang, co-founder, chairwoman and chief executive officer of BeyondSpring.

"Our commercial teams are very busy preparing for the potential near-term commercial launch of plinabulin in our first indication in the U.S. At the same time, we have strategically positioned plinabulin for commercial success in Greater China by partnering with Hengrui, the leading oncology R&D and commercial company in China with great synergy in its pipeline with plinabulin. We believe we are truly on the cusp of unlocking the tremendous potential of plinabulin to help many patients in need," Dr. Huang continued.

Recent Clinical and Corporate Highlights

DUBLIN-3 Study (2nd/3rd line NSCLC – EGFR wild type, a global, single-blinded randomized active controlled registrational study, Plinabulin + Docetaxel vs. Docetaxel alone, primary endpoint: Overall Survival):

Announced positive topline results of plinabulin in combination with docetaxel for the treatment of 2nd/3rd line non-small cell lung cancer (NSCLC) with EGFR wild type.

The data showed that, compared to docetaxel alone, the combination met the primary endpoint of increasing overall survival (mean OS, p=0.03; OS log-rank, p<0.04).
It also met key secondary endpoints, including significantly improving ORR, PFS, and 24- and 36-month OS (double OS rate vs. docetaxel) rates, and significant reduction in the incidence of Grade 4 neutropenia.
OS rate for 48 months is at 10.6% for plinabulin + docetaxel vs. 0% for docetaxel alone.
Greater China Partnership on Plinabulin with Hengrui, leading R&D and commercialization company in oncology products in China:
Announced an exclusive commercialization and co-development agreement between Jiangsu Hengrui Pharmaceuticals Co., Ltd. (or "Hengrui") and Wanchunbulin, BeyondSpring’s China subsidiary, for plinabulin in Greater China, the key terms of which are outlined below:

The NDA filing for plinabulin in China has been accepted with Priority Review for prevention of CIN.
Hengrui receives exclusive commercialization and co-development rights to plinabulin in all indications in Greater China.
BeyondSpring retains global rights outside of Greater China.
Wanchunbulin retains manufacturing rights and is entitled to receive the full amount of sales proceeds, and will pay Hengrui a pre-determined percentage of the net sales of plinabulin in Greater China.
Wanchunbulin to receive up to 1.3B RMB (est. US$200M), including an upfront payment of 200M RMB (est. US$30M) and regulatory and sales milestones of up to 1.1B RMB (est. US$170M).
Hengrui to pay all commercialization costs, and will pay 50% of clinical development costs for future indications after CIN and NSCLC.
Hengrui will make an equity investment of 100M RMB (est. US$15M) into Wanchunbulin at a pre-money valuation of 3.6B RMB (est. US$560M).

Plinabulin Triple IO combo in severe cancer indications (Phase 1 and phase 2 IIT Studies):
SCLC phase 1 data (plinabulin + Nivolumab + Ipilimumab) presented at ASCO (Free ASCO Whitepaper) (patients from US sites): 46% ORR for all 2nd/3rd line patients, and 43% for PD-L1 inhibitor failed patients (with long duration of treatment as long as 18 months).
Patients with 7 solid tumor types that failed PD-1/PD-L1 inhibitor at MD Anderson: first patient enrolled in June 2021. These 7 cancers include bladder cancer, melanoma, Merkel cell cancer, MSI-H Cancers (of any histology), NSCLC, renal cell cancer, and SCLC.
Added Board Member to strengthen commercial readiness for plinabulin
Strengthened its Board of Directors with the addition of Mr. Brendan Delaney, bringing significant expertise in commercial oncology drug launches.

Delaney currently serves as the Chief Commercial Officer of Constellation Pharma. Prior to this, he was the Chief Commercial Officer of Immunomedics, where he led the buildout of the marketing, sales, market access, and commercial operations teams.
Upcoming Milestones

September 20, 2021: ESMO (Free ESMO Whitepaper) Late-breaking oral presentation on DUBLIN-3
November 30, 2021: PDUFA date for plinabulin in CIN prevention
1H 2022: NDA Submission for plinabulin in NSCLC
2022: (Big Ten Cancer Research Consortium, Investigator Initiated study): Phase 2 Data expected in plinabulin + nivolumab + ipilimumab in checkpoint inhibitor-resistant SCLC.
2022: (MD Anderson investigator led study): Phase 1 Data expected in plinabulin + PD-1/PD-L1 inhibitors + radiation in patients with seven cancer types that failed PD-1/PD-L1.

Second Quarter Financial Results

Research and development ("R&D") expenses were $11.3 million for the quarter ended June 30, 2021, compared to $11.0 million for the quarter ended June 30, 2020. The increase was primarily due to higher personnel and non-cash stock-based compensation expenses, which were partially offset by lower clinical development expenses.
General and administrative ("G&A") expenses were $9.0 million for the quarter ended June 30, 2021, compared to $2.6 million for the quarter ended June 30, 2020. The $6.4 million increase was primarily due to higher personnel costs, non-cash stock-based compensation expense, and costs associated with plinabulin pre-commercialization activities.
Net loss attributable to the Company was $19.3 million for the quarter ended June 30, 2021, compared to $12.8 million for the quarter ended June 30, 2020.
As of June 30, 2021, the Company had cash, cash equivalents, and short-term investments of $76.3 million. The Company believes it has sufficient cash to support its ongoing clinical programs over the next year, including its immuno-oncology pipeline, and to prepare for a potential launch of plinabulin in CIN in early 2022.
Year-to-Date Financial Results

R&D expenses were $22.6 million for the six-month period ended June 30, 2021, compared to $24.7 million for the six-month period ended June 30, 2020. The $2.1 million decrease was primarily due to lower clinical development, regulatory and non-cash stock-based compensation expenses that were partially offset by higher personnel costs.
G&A expenses were $15.4 million for the six-month period ended June 30, 2021, compared to $5.5 million for the six-month period ended June 30, 2020. The $9.9 million increase was primarily due to higher personnel costs, non-cash stock-based compensation expense, as well as costs associated with plinabulin pre-commercialization activities.
Net loss attributable to the Company was $36.3 million for the six-month period ended June 30, 2021, compared to $28.8 million for the six-month period ended June 30, 2020.
Second Quarter 2021 Results Conference Call and Webcast Details

The management of BeyondSpring will host a conference call and webcast for the investment community today, September 10, 2021, at 8:00 am ET. The conference call can be accessed by dialing 877-451-6152 (U.S. and Canada) or +1-201-389-0879 (International). The passcode for the conference call is 13722968 To access the live webcast or subsequent archived recording, click here or visit the "investors" section of the BeyondSpring website at www.beyondspringpharma.com. The webcast will be recorded and available for replay on the company’s website for 90 days.

On September 09, 2021 Vor Biopharma, a clinical-stage cell and genome engineering company, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to VOR33, the Company’s lead engineered hematopoietic stem cell (eHSC) therapeutic candidate for the treatment of acute myeloid leukemia (AML) (Press release, PureTech Health, SEP 10, 2021, View Source [SID1234587506]).

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VOR33 consists of CRISPR genome-edited hematopoietic stem and progenitor cells that have been engineered to lack CD33. Once infused, VOR33 is designed to protect patients’ healthy cells from anti-CD33 therapies, such as VCAR33 or Mylotarg (gemtuzumab ozogamicin). VOR33 is intended to replace standard of care transplants for AML patients who are at high risk of relapse and has the potential to seamlessly integrate into current transplant settings.

"Receiving Fast Track designation is an important milestone for Vor, which signals the FDA’s recognition of the serious and life-threatening medical condition of patients facing acute myeloid leukemia and the potential of VOR33 to address this unmet medical need," said Robert Pietrusko, PharmD, Vor’s Chief Regulatory and Quality Officer. "We will continue to work closely with the FDA to expedite the development of VOR33, which is now actively enrolling in its Phase 1/2a clinical trial for AML patients who currently have limited treatment options. We continue to remain on-track to report VOR33’s initial clinical data in the first half of 2022."

VOR33 is the lead product candidate of Vor’s novel scientific platform, which has the mission to create next-generation, treatment-resistant transplants that unlock the potential of targeted cancer therapies by leveraging advances in cell therapy and gene editing. Vor is currently exploring the use of its genome engineered hematopoietic stem cell platform in combination with multiple therapeutic modalities.

Fast Track designation is intended to facilitate development and expedite review of products designed to treat serious and life-threatening conditions with unmet medical needs. The designation is granted upon the FDA’s review of data that demonstrate this potential, along with a product development program that is adequately designed to address the unmet medical need. Therapeutic candidates receiving Fast Track designation may be eligible for priority review and accelerated approval if certain conditions are met.

On September 9, 2021 PAQ Therapeutics ("PAQ"), a biotechnology company harnessing the power of autophagy to restore health and cure disease, and Insilico Medicine ("Insilico"), an end-to-end artificial intelligence (AI)-driven drug discovery company, reported that the companies have entered into a collaboration agreement to develop small molecule therapies designed to hijack the autophagy pathway to address novel disease targets (Press release, PAQ Therapeutics, SEP 9, 2021, View Source [SID1234649950]).

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Under the terms of the agreement, both parties will leverage Insilico’s small molecule compound generation platform Chemistry42 and other AI-powered drug discovery technologies in combination with PAQ’s autophagosome-tethering compound (ATTEC) technology platform to discover novel small molecules with the potential to catalyze and selectively enhance the degradation of disease-causing entities through autophagy.

Autophagy is the natural cellular degradation mechanism that removes unnecessary or dysfunctional components through a lysosome-dependent mechanism. With its powerful ATTEC technology platform, PAQ expands the therapeutic potential of autophagy to target not only disease-causing proteins, but also lipids, pathogens, and other substrates with the goal of restoring health. Insilico’s AI-powered drug discovery platforms utilize deep generative models, reinforcement learning, transformers, and other modern machine learning techniques to speed the generation of new molecular structures with specific properties, improving the efficiency and success of drug discovery.

"PAQ’s autophagy-dependent approach supports a pivotal moment in the evolution of drug discovery and design by expanding the ability to target the disease-causing substrates underlying diseases with limited or no treatment options," said Feng Ren, Ph.D., Chief Scientific Officer and Head of Drug R&D at Insilico. "Insilico is pleased to partner with PAQ Therapeutics to leverage our AI-driven drug discovery platforms in advancing drug R&D of ATTECs to address unmet medical needs."

"As part of PAQ’s ongoing efforts to therapeutically harness autophagy-dependent degradation, one key next step is to integrate cutting-edge technologies like AI that support our overall hit-finding and drug discovery strategy," said Nan Ji, Ph.D., Co-founder, President and CEO, PAQ Therapeutics. "We are excited to leverage Insilico’s deep expertise and proven track record in AI-driven drug discovery during a pivotal time in our company’s growth and progress."

On September 9, 2021 PharmAbcine Inc. (KOSDAQ: 208340ks), a clinical-stage biotech company focusing on the development of next-generation antibody therapeutics, reported it submitted a Patent Cooperation Treaty (PCT) application for the combination therapy of olinvacimab, the Company’s anti-VEGFR2 antibody, and KEYTRUDA (pembrolizumab), MSD’s anti-PD-1 antibody, for the treatment of cancer (Press release, PharmAbcine, SEP 9, 2021, View Source [SID1234649188]).

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The PCT application is an international application that preserves the priority date. The PCT is an international treaty that has over 150 Contracting States worldwide. It assists applicants in seeking patent protection internationally for their inventions, helps patent offices with their patent granting decisions, and facilitates public access to a wealth of technical information relating to those inventions.

The application, which was submitted jointly with MSD, is based on the Phase Ib olinvacimab and pembrolizumab combo trial in metastatic Triple-Negative Breast Cancer (mTNBC). According to the interim result presented at San Antonio Breast Cancer Symposium (SABCS) 2020, the combo therapy showed encouraging efficacy data, including 50% Overall Response Rate (ORR) and 67% Disease Control Rate (DCR) in the high-dose olinvacimab (16mg/kg) cohort (n=6pts).

mTNBC is a highly malignant type of cancer that shows a high recurrence rate within the first five years after the diagnosis. mTNBC accounts for 15-20% of all breast cancers and shows a 5-year survival rate of approximately 11%. Unlike some other breast cancers, mTNBC does not express estrogen or progesterone receptors or human epidermal growth factor receptor 2 (HER2), and it does not respond to existing cancer drugs designed to target these markers. mTNBC is very difficult to treat, and there are very few FDA approved treatment options for these patients.

Olinvacimab, an anti-VEGFR2 (Vascular Endothelial Growth Factor Receptor 2) fully human antibody, is the Company’s leading pipeline and is undergoing multiple global clinical trials. In early September 2021, PharmAbcine initiated a Phase II olinvacimab and pembrolizumab combo study for the treatment of mTNBC (metastatic Triple-Negative Breast Cancer) in Australia. Also, a Phase II olinvacimab mono study for bevacizumab-nonresponding rGBM (recurrent glioblastoma multiforme) patients at multiple sites in both US and Australia and two Phase Ib olinvacimab and pembrolizumab combo trials in mTNBC and rGBM in Australia are still ongoing.

"Submission of this patent application will be our first step in securing the novelty of the combo therapy." said Dr. Jin-San Yoo, CEO of PharmAbcine. "We will move onto getting our patent secured in multiple countries with great needs for a cancer treatment."

On September 9, 2021 Erasca, Inc. (Nasdaq: ERAS), a clinical-stage precision oncology company singularly focused on discovering, developing, and commercializing therapies for patients with RAS/MAPK pathway-driven cancers, reported dosing of the first patient in the HERKULES-2 Phase 1b/2 trial evaluating ERAS-007 in combination with various agents in patients with advanced non-small cell lung cancer (NSCLC) (Press release, Erasca, SEP 9, 2021, View Source [SID1234639383]).

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"As the foundation of Erasca’s lung cancer platform, HERKULES-2 is a master protocol designed to inhibit multiple oncogenic drivers of the RAS/MAPK pathway to address high unmet needs in lung cancer. Initially focused on patients with mutant EGFR or KRAS NSCLC, HERKULES-2 will further progress to evaluate other combinations targeting additional subtypes of NSCLC," said Jonathan E. Lim, M.D., Erasca’s chairman, CEO, and co-founder. "Erasca’s series of HERKULES trials also includes tissue-specific master protocols in gastrointestinal cancers and hematological malignancies as well as a tissue-agnostic trial, tailored to evaluate promising combinations to inhibit oncogenic signaling and prevent the emergence of resistance."

HERKULES-2 will initially examine the safety, tolerability, and preliminary efficacy of ERAS-007 in combination with osimertinib (TAGRISSO) in patients with advanced NSCLC harboring an epidermal growth factor receptor mutation (EGFRm). After a recommended dose is determined, the Phase 2 expansion portion will further evaluate the safety and efficacy of the combination in patients whose disease has developed resistance to osimertinib, a setting in which there are currently no approved targeted therapies. Future sub-studies of HERKULES-2 will explore ERAS-007 or the SHP2 inhibitor ERAS-601 in combination with other agents in patients with different mutational subtypes, including a KRAS G12C mutation.

ERAS-007, a potential best-in-class inhibitor of the extracellular signal-regulated kinases (ERK), targets the terminal node of the RAS/MAPK pathway. The broad applicability of ERAS-007 across a wide range of indications and tumor types was recently highlighted in a preclinical study published in Cell Reports Medicine, supporting durable ERK blockade and potent antiproliferative efficacy in both solid tumor and hematological malignancy cell lines. ERAS-007 demonstrated preferential anti-tumor activity for tumor types harboring mutant BRAF, KRAS, NRAS, or HRAS, as well as robust inhibitory activity across a range of mutant KRAS subtypes.

About ERAS-007
ERAS-007 is a potential best-in-class ERK1/2 inhibitor being investigated alone or in combination with different inhibitors targeting upstream nodes of the MAPK pathway as part of Erasca’s MAPKlamp strategy. The extracellular signal-regulated kinases (ERK), ERK1 and ERK2, belong to a family of serine-threonine kinases that regulate cellular signaling and comprise the terminal node of the RAS/MAPK pathway. The broad therapeutic potential of ERAS-007 is being investigated initially across four HERKULES clinical trials that span multiple tumor types and include both monotherapy and combinations with approved and investigational agents, such as RTK, SHP2, RAS, RAF, and/or cell cycle inhibitors. HERKULES-1, a Phase 1b/2 clinical trial for ERAS-007 as a single agent and in combination with the SHP2 inhibitor ERAS-601 (together, Erasca’s first MAPKlamp) in advanced solid tumors, and HERKULES-2, a Phase 1b/2 clinical trial for ERAS-007 in combination with various agents in patients with NSCLC, are currently enrolling patients. HERKULES-3, a Phase 1b/2 clinical trial for ERAS-007 in combination with various agents in patients with gastrointestinal cancers, is expected to begin by year-end. HERKULES-4, a Phase 1b/2 clinical trial for ERAS-007 in combination with various agents in patients with hematologic malignancies, is anticipated to begin in the first quarter of 2022.